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- 850 cancer cell lines screened in Broad Institute’s PRISM lab - - Rencofilstat active on 220 cancer cell lines spanning 86% of cancer types – EDISON, N.J., Sept. 21, 2023 (GLOBE NEWSWIRE) -- Hepion Pharmaceuticals, Inc. (NASDAQ:HEPA), a clinical stage biopharmaceutical company focused on Artificial Intelligence (“AI”)-driven therapeutic drug development for the treatment of non-alcoholic steatohepatitis (“NASH”), fibrotic diseases, hepatocellular carcinoma (“HCC”), and other chronic diseases, today announced results from a study with in which the anti-cancer activity of Hepion’s lead drug candidate, rencofilstat, was tested in a high through-put screen on 850 cancer cell lines spanning 28 types of cancer at the PRISM lab at the Broad Institute of MIT and Harvard. The Broad Institute is one of the few institutions in the world with such an expansive cancer cell line screening program. By utilizing advanced technologies and global collaborations, the Broad Institute has become a global leader in understanding cancer and other human diseases and helping to develop effective therapeutics. Rencofilstat was administered at eight concentrations to each cancer cell line in culture for 5 days, followed by measurement of surviving cells to determine how effectively the drug candidate killed or suppressed proliferation of the cancer cells. Defining “anti-cancer responsiveness” as 50% or greater reduction in viability following treatment, 26% of all tested cancer cell lines (220/850) spanning 86% of cancer cell types (24/28) were responsive to rencofilstat. Some of the rencofilstat-sensitive cell lines were HCC cells, which further supports Hepion’s plans for a clinical trial in this indication. Furthermore, the reductions in viability in responsive cells occurred at drug concentrations similar to those observed in individuals participating in Hepion’s NASH clinical trials. Thus, administration of rencofilstat to cancer patients with the standard regimen of once-daily oral dosing may be efficacious for those with responsive types of cancer. The screening study also integrated additional information collected by the Broad Institute about the cancer cell lines, such as gene mutations, gene expression, and protein and metabolic profiles, to provide insights into rencofilstat’s mechanisms of action and identify biomarkers associated with its anti-cancer activity. Some of the markers uncovered by these analyses were related to familiar rencofilstat mechanisms, whereas others pointed to new processes. Genes known to be mutated in HCC or other types of cancer, including ATM, PTPRB, HNF1A, NOTCH1, ALK, TP63, IDH2 and MAP3K, were among the many genes identified to possibly influence the sensitivity of cells to rencofilstat. “The results from this high-throughput screen provide valuable insights into how rencofilstat directly arrests cancer cells and adds to the discoveries being made from our in-house research. These direct effects on cancer cell lines may be an important part of rencofilstat’s anti-cancer activity,” remarked Daren Ure, Hepion’s Chief Scientific Officer. “We have already observed that rencofilstat fights cancer through other indirect mechanisms, and in particular by changing the tissue environment in which the tumor grows. For example, we previously found that rencofilstat altered the immune cell composition of liver tumors in mice, suggesting an enhanced immune attack on the tumors. Directly targeting cancer cells while simultaneously modulating their microenvironment provides additional weapons for attacking cancer. Our ongoing research aims to further define the characteristics of liver cancer and other types of cancer that make them most susceptible to rencofilstat, and to thereby help identify who may benefit most from treatment.” About Hepion Pharmaceuticals The Company's lead drug candidate, rencofilstat, is a potent inhibitor of cyclophilins, which are involved in many disease processes. Rencofilstat has been shown to reduce liver fibrosis and hepatocellular carcinoma tumor burden in experimental disease models and is currently in Phase 2 clinical development for the treatment of NASH. In November 2021, the U.S. Food and Drug Administration (“FDA”) granted Fast Track designation for rencofilstat for the treatment of NASH. That was followed in June 2022 by the FDA’s granting of Orphan Drug designation to rencofilstat for the treatment of HCC. Hepion has created a proprietary Artificial Intelligence deep machine learning (“AI/ML”) platform designed to better understand disease processes and identify patients that are rencofilstat responders. This AI/ML has the potential to shorten development timelines and increase the observable differences between placebo and treatment groups. In addition, Hepion’s AI/ML can be used to drive its ongoing NASH and HCC clinical development programs and identify other potential therapeutic indications for cyclophilin inhibition with rencofilstat. Forward-Looking Statements Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimated,” and “intend,” among others. These forward-looking statements are based on Hepion Pharmaceuticals’ current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, substantial competition; our ability to continue as a going concern; our need for additional financing; uncertainties of patent protection and litigation; risks associated with delays, increased costs and funding shortages caused by the COVID-19 pandemic; uncertainties with respect to lengthy and expensive clinical trials, that results of earlier studies and trials may not be predictive of future trial results; uncertainties of government or third party payer reimbursement; limited sales and marketing efforts and dependence upon third parties; and risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations. As with any drug candidates under development, there are significant risks in the development, regulatory approval, and commercialization of new products. There are no guarantees that future clinical trials discussed in this press release will be completed or successful, or that any product will receive regulatory approval for any indication or prove to be commercially successful. Hepion Pharmaceuticals does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in Hepion Pharmaceuticals’ Form 10-K for the year ended December 31, 2022, and other periodic reports filed with the Securities and Exchange Commission. For further information, please contact: Stephen KilmerHepion Pharmaceuticals Investor RelationsDirect: (646) 274-3580skilmer@hepionpharma.com

CINCINNATI, Jan. 05, 2021 (GLOBE NEWSWIRE) -- Aerpio Pharmaceuticals, Inc. (“Aerpio” or the “Company”) (Nasdaq: ARPO), a biopharmaceutical company focused on developing compounds that activate Tie2, today announced that its Board of Directors has initiated a process to explore and review a range of strategic alternatives focused on maximizing stockholder value from the Company’s clinical assets and cash resources, which amounted to $47.3 million as of September 30, 2020. As part of this process, the Company will explore strategic options for partnering its programs, as well as, the potential for an acquisition, company sale, merger, business combination, asset sale, in-license, out-license or other strategic transaction. Ladenburg Thalmann & Co. Inc. will continue to act as Aerpio’s financial advisor with respect to the strategic review process. There can be no assurance that this exploration of strategic alternatives will result in the Company entering or completing any transaction. Aerpio programs to be incorporated into this review include: Phase 2 program of razuprotafib in glaucoma: a recently completed a Phase 2 trial in glaucoma patients showed that the change from baseline in diurnal mean IOP at Day 28 of study eyes treated with razuprotafib BID plus latanoprost was statistically significant (two-sided p-value 0.0130 and LS mean difference of -0.92 mmHg) compared to those treated with latanoprost monotherapy. Further analysis of the results demonstrated that razuprotafib had a larger IOP reduction after longer duration dosing (28 days versus 14 days) consistent with its potential mechanism of repairing Schlemm’s canal. Razuprotafib also produced larger IOP reductions in patients with higher starting IOP, or a 1.6 mmHg IOP reduction in patients with post wash-out IOP’s of >26 mmHg. The razuprotafib topical drops were well tolerated in this trial. a recently completed a Phase 2 trial in glaucoma patients showed that the change from baseline in diurnal mean IOP at Day 28 of study eyes treated with razuprotafib BID plus latanoprost was statistically significant (two-sided p-value 0.0130 and LS mean difference of -0.92 mmHg) compared to those treated with latanoprost monotherapy. Further analysis of the results demonstrated that razuprotafib had a larger IOP reduction after longer duration dosing (28 days versus 14 days) consistent with its potential mechanism of repairing Schlemm’s canal. Razuprotafib also produced larger IOP reductions in patients with higher starting IOP, or a 1.6 mmHg IOP reduction in patients with post wash-out IOP’s of >26 mmHg. The razuprotafib topical drops were well tolerated in this trial. Phase 2 program of razuprotafib in COVID-19: the Company has two ongoing clinical trials of razuprotafib to prevent or mitigate acute respiratory distress syndrome (ARDS) in COVID-19 patients where patient enrollment and dosing continues. If successful, these trials may open the door to treating ARDS across a broader array of infections. the Company has two ongoing clinical trials of razuprotafib to prevent or mitigate acute respiratory distress syndrome (ARDS) in COVID-19 patients where patient enrollment and dosing continues. If successful, these trials may open the door to treating ARDS across a broader array of infections. Preclinical Tie2 activating antibodies: the Company also has Tie2 activating antibodies in early development, including both a monospecific antibody that may be used to treat diabetic complications, and a bispecific antibody that may be used to treat retinal diseases such as diabetic macular edema (DME) and wet age related macular edema (wAMD). Aerpio does not intend to make any further disclosures regarding the strategic review process unless and until specific actions are approved. About Aerpio Pharmaceuticals Aerpio Pharmaceuticals, Inc. is a biopharmaceutical company focused on developing compounds that activate Tie2 to treat ocular diseases and diabetic complications, as well as other indications in which the Company believes that activation of Tie2 may have therapeutic potential, including acute respiratory distress syndrome (“ARDS”) associated with COVID-19 infections. Recently published mouse and human genetic data implicate the Angpt/Tie2 pathway in maintenance of Schlemm’s canal, a critical component of the conventional outflow tract. The Company’s lead compound, razuprotafib (formerly AKB-9778), a first-in-class small molecule inhibitor of vascular endothelial protein tyrosine phosphatase (“VE-PTP”), is being developed as a potential treatment for open angle glaucoma, and the Company intends to investigate the therapeutic potential of razuprotafib in other indications. The Company is also evaluating development options for ARP-1536, a humanized monoclonal antibody, for its therapeutic potential in the treatment of diabetic vascular complications including nephropathy and diabetic macular edema (“DME”). The Company’s third asset is a bispecific antibody that binds both VEGF and VE-PTP which is designed to inhibit VEGF activation and activate Tie2. This bispecific antibody has the potential to be an improved treatment for wet age-related macular degeneration and DME via intravitreal injection. Finally, the Company has exclusively out-licensed AKB-4924 (now called GB004), a first-in-class small molecule inhibitor of hypoxia-inducible factor-1 (HIF). GB004 is being developed by AKB-4924’s exclusive licensor, Gossamer Bio, Inc. For more information, please visit . About Razuprotafib (formerly known as AKB-9778) Razuprotafib binds to and inhibits vascular endothelial protein tyrosine phosphatase (“VE-PTP”), an important negative regulator of Tie2. Decreased Tie2 activity contributes to vascular instability in many diseases including diabetes and more recently has been shown to contribute to the development of increased IOP and glaucoma. Razuprotafib activates the Tie2 receptor irrespective of extracellular levels of its binding ligands, angiopoietin-1 (agonist) or angiopoietin-2 (antagonist) and we believe that it may be the most efficient pharmacologic approach to maintain normal Tie2 activation. Aerpio is studying a topical ocular formulation of razuprotafib in open angle glaucoma and exploring the utility of subcutaneous razuprotafib for diabetic complications, including diabetic nephropathy. In addition, a subcutaneous formulation of razuprotafib is being explored for its therapeutic potential in treating or preventing ARDS associated with COVID-19. Forward Looking Statements This press release contains forward-looking statements. Statements in this press release that are not purely historical are forward-looking statements. Such forward-looking statements include, among other things, the Company’s strategic alternatives review process and the potential transactions that may be identified and explored as a result of that process, the Company’s product candidates, including razuprotafib, ARP-1536 and the bispecific antibody asset, the clinical development plan therefor, and the therapeutic potential thereof, the Company’s plans and expectations with respect to razuprotafib and the development therefor and therapeutic potential thereof in addressing COVID-19 and ARDS related thereto and the intended benefits from the Company’s collaboration with Gossamer Bio for GB004, including the continued development of GB004 and the milestone and royalty payments related to the collaboration. Actual results could differ from those projected in any forward-looking statements due to several risk factors. Such factors include, among others, the ability to identify and consummate strategic alternatives that yield additional value for shareholders; the timing, benefits and outcome of the Company's strategic alternatives review process, including the determination of whether or not to pursue or consummate any strategic alternative; the structure, terms and specific risks and uncertainties associated with any potential strategic transaction; potential disruptions in our business and the stock price as a result of our exploration, review and pursuit of strategic alternatives or the public announcement thereof and any decision or transaction resulting from such review; the continued development of GB004 and maintaining and deriving the intended benefits of the Company’s collaboration with Gossamer Bio; ability to continue to develop razuprotafib or other product candidates, including in indications related to COVID-19; our review and evaluation of strategic plans for our razuprotafib glaucoma program; the inherent uncertainties associated with the drug development process, including uncertainties in regulatory interactions, the design of planned or future clinical trials, commencing clinical trials and enrollment of patients in clinical trials; obtaining any necessary regulatory clearances in order to commence and conduct planned or future clinical trials; the impact of the ongoing COVID-19 pandemic on the Company’s business operations, including research and development efforts and the ability of the Company to commence, conduct and complete its planned clinical activities; and competition in the industry in which the Company operates and overall market conditions; and the additional factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2019, as updated by our subsequent Quarterly Reports on Form 10-Q and our other subsequent filings with the SEC. These forward-looking statements are made as of the date of this press release, and the Company assumes no obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those projected in the forward-looking statements, except as required by law. Investors should consult all the information set forth herein and should also refer to the risk factor disclosure set forth in the reports and other documents the Company files with the SEC available at . Contacts Investors & Media: Aerpio Pharmaceuticals, Inc. Gina Marek VP Finance gmarek@aerpio.com Or Investors : Irina Koffler LifeSci Advisors ikoffler@lifesciadvisors.com Source: Aerpio Pharmaceuticals, Inc.

It was a busy week for both COVID-19-related clinical trial news and the rest of the industry. Here’s a look. It was a busy week for both COVID-19-related clinical trial news and the rest of the industry. Here’s a look. COVID-19-Related Vir Biotechnology and GlaxoSmithKline dosed the first patient last week in a Phase II/III clinical trial of VIR-7831, a fully human monoclonal antibody against COVID-19. The trial is evaluating therapy as early treatment for COVID-19 patient at high risk of hospitalization. The Vir-GSK COMET-ICE study plans to enroll about 1,300 patients globally who have early symptoms of infection. The goal is to evaluate VIR-7831, a single-dose monoclonal antibody, to see if it can prevent hospitalization from the disease. They expect results before the end of the year with complete data in the first quarter of 2021, and possibly early access to treatment in the first half of 2021. FSD Pharma submitted an IND for FSD201 (ultramicronized palmitoylethanolamide, or ultramicronized PEA) to treat COVID-19. FSD201 is being developed for its anti-inflammatory properties to avoid the cytokine storm linked with acute lung injury in hospitalized COVID-19 patients. The Phase II trial will be run at 25 to 30 sites in North America. Orpheris , a subsidiary of Ashvattha Therapeutics, enrolled the first patients in its Phase II PRANA clinical trial of OP-101 in severe COVID-19. OP-101 is designed to target and shut down all proinflammatory pathways and restore macrophages to a normal, anti-inflammatory state. AstraZeneca announced that its Phase III clinical trial of its COVID-19 vaccine candidate, AZD1222, is expanding into the U.S. It will be dubbed D8110C00001 and is funded by the Biomedical Advanced Development Authority (BARDA) and the National Institute of Allergy and Infectious Diseases (NIAID). The NIAID-supported COVID-19 Prevention Network (CoVPN) is also participating. The U.S. expansion will recruit up to 30,000 adults over the age of 18 years from a broad range of racial, ethnic and geographic groups who are healthy or have stable underlying medical conditions. This will also include patients with HIV, who are at increased risk from COVID-19 infections. Clear Creek Bio dosed the first patient in a Phase I clinical trial of brequinar in COVID-19 patients. Brequinar is an oral, potent and selective small molecule DHODH inhibitor that blocks host cell de novo pyrimidine biosynthesis, which is needed for DNA and RNA synthesis. It appears to have potent antiviral activity. Biophytis enrolled the first patient in COVA, a Phase II/III trial of sarconeos (BIO101) for patients with COVID-19-related respiratory failure. It has five centers recruiting patients in Belgium, France and the U.S. Sarconeos is an oral small molecule being developed in Phase IIb in sarcopenia, as well as Duchenne muscular dystrophy (DMD). The drug activates the MAS receptor, a key component of the protective arm of RAS, the renin angiotensin system, which plays a key role in regulating respiratory function. Sanofi announced that its Phase III trial of IV Kevzara (sarilumab) at a dose of 200mg or 400mg in severely or critically ill patients hospitalized with COVID-19 did not meet its primary endpoint and key secondary endpoint compared to placebo. Kevzara is approved to treat adults with moderately to severely active rheumatoid arthritis. It binds to the IL-6b receptor and inhibits IL-6 mediated signaling. INmune Bio got the go-ahead from the FDA to initiate a Phase II trial of Quellor, a selective soluble tumor necrosis factor (sTNF) inhibitor, for the immune mediated complications in COVID-19 patients. The blinded randomized Phase II trial will enroll 366 COVID-19 patients in two equal sized cohorts, standard of care, which may include remdesivir, or SOC plus Quellor. A second dose of Quellor may be given a week later if the patient remains hospitalized. Organicell Regenerative Medicine reported that the FDA granted emergency, expanded access to treat two mild to moderate COVID-19 patients and one “long hauler” post COVID-19 patient with Zofin. The company plans to begin patient enrollment in a Phase I/II trial to evaluate the drug in moderate to severe COVID-19 patients. Zofin is a nanoparticle-based therapy derived from perinatal sources and designed to retain microRNAs. Aerpio Pharmaceuticals and Quantum Leap Healthcare Collaborative dosed the first patient with razuprotafib in the Phase II I-SPY COVID Trial in hopes of improving ARDs in severely ill COVID-19 patients. Razuprotafib is a first-in-class small molecule inhibitor of vascular endothelial protein tyrosine phosphatase and is also being developed for open angle glaucoma and other indications. City of Hope is initiating a Phase I trial of rheumatoid arthritis drug leflunomide in COVID-19 patients. Patients treated for cancer in the last two years may also be eligible. The overall focus is on cancer patients who are being treated for COVID-19. GlaxoSmithKline and Sanofi are beginning a Phase I/II clinical trial of their COVID-19 vaccine that uses GSK’s pandemic adjuvant technology. It will include 440 healthy adults be run at 11 separate sites. Non-COVID-19-Related AstraZeneca ’s Farxiga (dapagliflozin) dramatically prolonged survival in patients with chronic kidney disease in a Phase III clinical trial. Specifically, Farxiga with standard of care decreased the composite measure of worsening of renal function or risk of cardiovascular (CV) or renal death by 39% compared to placebo. This was in patients with chronic kidney disease (CKD) Stages 2-4 and elevated urinary albumin excretion. There were no differences observed in patients who had or did not have type 2 diabetes. Akcea Therapeutics and Ionis Pharmaceuticals presented data from the Phase II study of AKCEA-APOCIII-LRx. The therapy met primary and key secondary endpoints with significant decreases in triglyceride and apoC-III levels. AKCEA-APOCIII-LRx is designed using Ionis’ Ligand Conjugated Antisense (LICA) technology platform to inhibit production of apolipoprotein C-III, a protein generated in the liver that plays a primary role in the regulation of serum triglycerides. UCB published the results of the Phase III VIMPAT (lacosamide) CV as adjunctive treatment for uncontrolled primary generalized tonic-clonic seizures (PGTCS). The trial enrolled 242 patients with idiopathic generalized epilepsy. The primary endpoint was time to second PGTCS during the 24-week treatment period. Treatment with locasamide demonstrated a significantly lower risk of developing a second PGTCS and a significantly higher rate of freedom from PGTCS during the period compared to placebo. It was approved in the U.S. in 2008 as an add-on therapy for adult patients, then as a monotherapy in adults in August 2014, and in 2018, as monotherapy or adjunctive therapy in patients four years of age and older with partial-onset seizures. Eisai announced data from several post hoc analyses of Dayvigo from the Phase III SUNRISE 1 and 2 trials and topline results from an open label pilot study. The studies evaluated the transition of insomnia patients from zolpidem to Dayvigo, with generally positive results. Dayvigo (Lemborexant) is a small-molecule orexin receptor antagonist. Novartis announced results from a post-hoc analysis of pooled data from the Phase III ORION-10 and -11 trials evaluating individual responses of patients on low-density lipoprotein cholesterol reduction with inclisiran. Inclisiran is a first-in-class investigation treatment for hyperlipidemia in adults. The new data showed a highly consistent effect with a similar safety pro placebo. Boehringer Ingelheim and Eli Lilly announced full results from the EMPEROR-Reduced Phase III trial in adults with heart failure with reduced ejection fraction, with and without diabetes. This showed that Jardiance (empagliflozin) was associated with a 25% relative risk reduction in the primary endpoint of time to cardiovascular death or hospitalization due to heart failure. Acasti Pharma announced topline data from its Phase III TRILOGY 2 trial of CaPre (omega-3 phospholipid) to reduce severe triglyceride levels. The primary endpoint was triglyceride reduction at 12 and 26 weeks. The trial evaluated 278 patients. Patients receiving CaPre demonstrated a 30.4% median reduction in triglyceride levels compared to 30.5% in TRILOGY 1, and a 17.9% median reduction in triglyceride levels in patients receiving placebo at 12 weeks compared to 27.5% in TRILOGY 1. The company indicated that the unadjusted, placebo corrected triglyceride reduction of 12.4% achieved a “p” value of 0.19, which was not statistically significant—as a result, TRILOGY 2 did not meet the primary endpoint. Mirum Pharmaceuticals presented new data from its Phase II INDIGO trial. It was a five-year analysis that demonstrated that patients with PFIC2, also called bile salt export pump (BSEP) deficiency, who achieved serum bile acid (sBA) control on long-term maralixibat treatment have a significant improvement in transplant-free survival. Bristol Myers Squibb announced interim data from the Phase III open-label extension trial DAYBREAK. The data demonstrated the long-term efficacy and safety pro Zeposia (ozanimod) in relapsing forms of multiple sclerosis (MS). The trial included 2,494 patients who had previously completed a Phase I, II or III Zeposia trial and who had an average treatment time of 35.4 months while in DAYBREAK. No new safety concerns were observed. At 2 and 3 years, 79% and 75% of patients, respectively, were relapse-free and 3- and 6-month confirmed disability progression was observed in 10.8% and 8.6% of participants, respectively. Oxurion NV dosed the first patient in its two-part Phase II trial KALAHARI. It is evaluating THR-149 for the treatment of diabetic macular edema (DME). THR-149 acts via inhibition of the Plasma Kallikrein-Kinin (PKal-Kinin) system, a validated VEGF independent target for DME. Janssen Pharmaceutical of Johnson & Johnson made a strategic call to halt development of pimodivir, an antiviral treatment for influenza A. The decision was based on data from a pre-planned interim analysis of the Phase III trial of pimodivir in hospitalized influenza A patients. The analysis suggested that the drug in combination with standard of care (SOC) was “very unlikely” to show added benefit in the patient population over SOC alone. Akebia Therapeutics announced topline results for PRO 2 TECT, the second of two Phase III cardiovascular outcomes programs. The trial was evaluating the company’s vadadustat for treatment of anemia caused by chronic kidney disease in adults not on dialysis. In the two PRO 2 TECT studies, vadadustat hit the primary and key secondary efficacy endpoint, which was non-inferiority to darbepoetin alfa. This was measured by a mean change in hemoglobin (Hb) between baseline and the primary evaluation period, weeks 24 to 36 and the secondary evaluation period at weeks 40 to 52. However, the drug did not meet the primary safety endpoint of the PRO 2 TECT program. This was defined as non-inferiority of vadadustat compared to darbepoetin alfa in how long to the first occurrence of major adverse cardiovascular events (MACE). MACE is the composite of all-cause mortality, non-fatal myocardial infarction, and non-fatal stroke. Amylyx Pharmaceuticals published data from its Phase II/III CENTAUR clinical trial evaluating AMX0035 in amyotrophic lateral sclerosis (ALS). The research was published in the New England Journal of Medicine. The trial met its primary endpoint, showing a clinically meaningful and statistically significant treatment benefit based on the Revised ALS Functional Rating Scale (ALSFRS-R). The trial evaluated 137 people with ALS and was conducted at 25 medical centers in the U.S. through the Northeast ALS (NEALS) consortium. AMX0035 is a neuroprotective therapy designed to decrease neuronal death and dysfunction. It targets endoplasmic reticulum and mitochondrial dependent neuronal degeneration pathways in ALS.