CK1ε

Researchers have identified a new pathological mechanism for a familial type of Parkinson's disease caused by a mutation in the CHCHD2 gene. Mutant CHCHD2 protein is mislocalized in cells and leads to alpha-synuclein protein aggregates via interactions with another protein, known as Csnk1e/d. These findings indicate that Csnk1e/d inhibition may slow or halt Parkinson's disease development in patients with CHCHD2 mutations, providing new hope for affected families. Parkinson's disease, characterized by various motor dysfunctions, is the second most common neurodegenerative disorder in the world. It is known that specific gene mutations that are passed down through families are responsible for some cases of Parkinson's disease. But now, researchers from Japan have found that this might open the doors to new therapies. In a study published recently in EMBO Molecular Medicine, researchers from Tokyo Medical and Dental University (TMDU) have identified the cellular processes that likely lead to Parkinson's disease in patients with mutations in a specificgene. Motor disorders seen in Parkinson's disease are caused by the death of cells that produce dopamine -- an important molecule for cellular communication -- in a brain region known as the substantia nigra. In this region, protein aggregates containing a protein known as alpha-synuclein form. However, the exact cause and the process remains unknown. Researchers from TMDU decided to investigate these mechanisms in a familial form of Parkinson's disease caused by mutations in CHCHD2, a gene encoding a specific domain containing two CHCHD2 proteins. To do this, they induced a CHCHD2 mutation in both cell cultures and mice. "When we looked at normal CHCHD2 protein in cells, it was located in the mitochondria, which provides energy to the cell," says lead author of the study Satoru Torii. "But the mutant CHCHD2 was expressed in a very different area -- in the cell cytosol, where it recruited another protein known as casein kinase 1 epsilon/delta (Csnk1e/d) and led to the aggregation of phosphorylated alpha-synuclein and neurofilaments." Because the mutant CHCHD2 caused Parkinson's disease-related pathology in cells, the researchers investigated its effects in mice using two different methods of expressing mutant CHCHD2. All mice with CHCHD2 mutation had motor impairments, and their brains showed mislocalized CHCHD2 and aggregated alpha-synuclein in the dopamine-producing cells of the substantia nigra. The same observations were made when the research team looked at a postmortem brain of a patient with Parkinson's disease caused by a CHCHD2 mutation, and in laboratory cell cultures harvested from another patient. "The most exciting finding for us was that, when we inhibited the associated protein Csnk1e/d, we saw motor improvements and fewer Parkinson's disease-related symptoms in the Parkinson's disease model mice, as well as less pathology in cells grown from a patient with a CHCHD2 gene mutation," explains Shigeomi Shimizu, senior author of the study. "This suggests that it may be possible to delay -- or even prevent -- Parkinson's disease development in people with this mutation." Given that there are currently no treatments that effectively slow or halt the progression of Parkinson's disease, the findings of this study are very encouraging, especially for patients with CHCHD2 mutations. The results also improve our understanding of how Parkinson's disease can develop in the brain and bring hope to all patients and their families.

NEW YORK, Aug. 9, 2022 /PRNewswire/ -- Pomerantz LLP announces that a class action lawsuit has been filed against TG Therapeutics, Inc. ("TG Therapeutics" or the "Company") (NASDAQ: TGTX) and certain of its officers. The class action, filed in the United States District Court for the Southern District of New York, and docketed under 22-cv-06106, is on behalf of a class consisting of all persons and entities other than Defendants that purchased or otherwise acquired TG Therapeutics securities between January 15, 2020 and May 31, 2022, both dates inclusive (the "Class Period"), seeking to recover damages caused by Defendants' violations of the federal securities laws and to pursue remedies under Sections 10(b) and 20(a) of the Securities Exchange Act of 1934 (the "Exchange Act") and Rule 10b-5 promulgated thereunder, against the Company and certain of its top officials. If you are a shareholder who purchased or otherwise acquired TG Therapeutics securities during the Class Period, you have until September 16, 2022 to ask the Court to appoint you as Lead Plaintiff for the class. A copy of the Complaint can be obtained at . To discuss this action, contact Robert S. Willoughby at [email protected] or 888.476.6529 (or 888.4-POMLAW), toll-free, Ext. 7980. Those who inquire by e-mail are encouraged to include their mailing address, telephone number, and the number of shares purchased. [Click here for information about joining the class action] TG Therapeutics, a commercial stage biopharmaceutical company, focuses on the acquisition, development, and commercialization of novel treatments for B-cell malignancies and autoimmune diseases. The Company's therapeutic product candidates include Ublituximab, an investigational glycoengineered monoclonal antibody for the treatment of B-cell non-hodgkin lymphoma, chronic lymphocytic leukemia ("CLL"), and relapsing forms of multiple sclerosis; and Umbralisib, or UKONIQ, an oral inhibitor of PI3K-delta and CK1-epsilon for the treatment of CLL, marginal zone lymphoma, and follicular lymphoma. In January 2020, TG Therapeutics initiated a rolling submission of a New Drug Application ("NDA") to the U.S. Food and Drug Administration ("FDA"), requesting accelerated approval of Umbralisib as a treatment for patients with previously treated marginal zone lymphoma ("MZL") and follicular lymphoma ("FL") (the "Umbralisib MZL/FL NDA"). In December 2020, TG Therapeutics initiated a rolling submission of a Biologics License Application ("BLA") to the FDA for Ublituximab in combination with Umbralisib (together, "U2"), as a treatment for patients with CLL (the "U2 BLA"). In May 2021, TG Therapeutics submitted a supplemental New Drug Application ("sNDA") for Umbralisib to add an indication for CLL and small lymphocytic lymphoma ("SLL") in combination with Ublituximab (the "U2 sNDA"). In September 2021, TG Therapeutics submitted a BLA to the FDA for Ublituximab as a treatment for patients with relapsing forms of multiple sclerosis ("RMS") (the "Ublituximab RMS BLA"). The complaint alleges that throughout the Class Period, Defendants made materially false and misleading statements regarding the Company's business, operations, and compliance policies. Specifically, Defendants made false and/or misleading statements and/or failed to disclose that: (i) clinical trials revealed significant concerns related to the benefit-risk ratio and overall survival data of Ublituximab and Umbralisib; (ii) accordingly, it was unlikely that the Company would be able to obtain FDA approval of the Umbralisib MZL/FL NDA, the U2 BLA, the U2 sNDA, or the Ublituximab RMS BLA in their current forms; (iii) as a result, the Company had significantly overstated Ublituximab and Umbralisib's clinical and/or commercial prospects; and (iv) therefore, the Company's public statements were materially false and misleading at all relevant times. On November 30, 2021, TG Therapeutics issued a press release "announc[ing] the U.S. Food and Drug Administration (FDA) has notified the Company that it plans to host a meeting of the Oncologic Drugs Advisory Committee (ODAC) in connection with its review of the pending Biologics License Application (BLA)/supplemental New Drug Application (sNDA) for the combination of ublituximab and UKONIQ® (umbralisib) (combination referred to as U2) for the treatment of adult patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL)." TG Therapeutics advised that "[t]he FDA has notified the Company that potential questions and discussion topics for the ODAC include: the benefit-risk of the U2 combination in the treatment of CLL or SLL, and the benefit-risk of UKONIQ in relapsed/refractory marginal zone lymphoma (MZL) or follicular lymphoma (FL). In addition, as part of the benefit-risk analysis, the overall safety profile of the U2 regimen, including adverse events (serious and Grade 3-4), discontinuations due to adverse events, and dose modifications, is expected to be reviewed", stating that "[t]he FDA's concern giving rise to the ODAC meeting appears to stem from an early analysis of overall survival from the UNITY-CLL trial." On this news, TG 'Therapeutics' stock price fell $8.16 per share, or 34.93%, to close at $15.20 per share on November 30, 2021. Then, on April 15, 2022, TG Therapeutics issued a press release "announc[ing] that the Company has voluntarily withdrawn the pending Biologics License Application (BLA)/supplemental New Drug Application (sNDA) for the combination of ublituximab and UKONIQ® (umbralisib) (combination referred to as U2) for the treatment of adult patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL)." The press release stated that "[t]he decision to withdraw was based on recently updated overall survival (OS) data from the UNITY-CLL Phase 3 trial that showed an increasing imbalance in OS." On this news, TG Therapeutics' stock price fell $1.93 per share, or 21.81%, to close at $6.92 per share on April 18, 2022. Then, on May 31, 2022, TG Therapeutics issued a press release announcing that the FDA extended the Prescription Drug User Fee Act date for Ublituximab to December 28, 2022 "to allow time to review a submission provided by the Company in response to an FDA information request, which the FDA deemed a major amendment." On this news, TG Therapeutics' stock price fell $0.75 per share, or 14.51%, to close at $4.42 per share on May 31, 2022. Finally, on June 1, 2022, the FDA announced that, due to safety concerns, it had withdrawn its approval for Umbralisib for the treatment of MZL and FL. Specifically, the FDA provided that "[u]pdated findings from the UNITY-CLL clinical trial continued to show a possible increased risk of death in patients receiving [UKONIQ]. As a result, we determined the risks of treatment with [UKONIQ] outweigh its benefits." On this news, TG 'Therapeutics' stock price fell $0.51 per share, or 11.53%, to close at $3.91 per share on June 1, 2022. Pomerantz LLP, with offices in New York, Chicago, Los Angeles, Paris, and Tel Aviv, is acknowledged as one of the premier firms in the areas of corporate, securities, and antitrust class litigation. Founded by the late Abraham L. Pomerantz, known as the dean of the class action bar, Pomerantz pioneered the field of securities class actions. Today, more than 85 years later, Pomerantz continues in the tradition he established, fighting for the rights of the victims of securities fraud, breaches of fiduciary duty, and corporate misconduct. The Firm has recovered numerous multimillion-dollar damages awards on behalf of class members. See CONTACT: Robert S. Willoughby Pomerantz LLP [email protected] 888-476-6529 ext. 7980 SOURCE Pomerantz LLP

NEW YORK, July 29, 2022 /PRNewswire/ -- WHY: Rosen Law Firm, a global investor rights law firm, reminds purchasers of the securities of TG Therapeutics, Inc. (NASDAQ: TGTX) between January 15, 2020 and May 31, 2022, both dates inclusive (the "Class Period"), of the important September 16, 2022 lead plaintiff deadline. SO WHAT: If you purchased TG Therapeutics securities you may be entitled to compensation without payment of any out of pocket fees or costs through a contingency fee arrangement. WHAT TO DO NEXT: To join the TG Therapeutics class action, go to or call Phillip Kim, Esq. toll-free at 866-767-3653 or email [email protected] or [email protected] for information on the class action. A class action lawsuit has already been filed. If you wish to serve as lead plaintiff, you must move the Court no later than September 16, 2022. A lead plaintiff is a representative party acting on behalf of other class members in directing the litigation. WHY ROSEN LAW: We encourage investors to select qualified counsel with a track record of success in leadership roles. Often, firms issuing notices do not have comparable experience, resources or any meaningful peer recognition. Many of these firms do not actually handle securities class actions, but are merely middlemen that refer clients or partner with law firms that actually litigate the cases. Be wise in selecting counsel. The Rosen Law Firm represents investors throughout the globe, concentrating its practice in securities class actions and shareholder derivative litigation. Rosen Law Firm has achieved the largest ever securities class action settlement against a Chinese Company. Rosen Law Firm was Ranked No. 1 by ISS Securities Class Action Services for number of securities class action settlements in 2017. The firm has been ranked in the top 4 each year since 2013 and has recovered hundreds of millions of dollars for investors. In 2019 alone the firm secured over $438 million for investors. In 2020, founding partner Laurence Rosen was named by law360 as a Titan of Plaintiffs' Bar. Many of the firm's attorneys have been recognized by Lawdragon and Super Lawyers. DETAILS OF THE CASE: According to the lawsuit, throughout the Class Period, defendants made false and/or misleading statements and/or failed to disclose that: (1) clinical trials revealed significant concerns related to the benefit-risk ratio and overall survival data of Ublituximab (an investigational glycoengineered monoclonal antibody for the treatment of B-cell non-hodgkin lymphoma, chronic lymphocytic leukemia ("CLL"), and relapsing forms of multiple sclerosis) and Umbralisib (or UKONIQ, an oral inhibitor of PI3K-delta and CK1-epsilon for the treatment of CLL, marginal zone lymphoma, and follicular lymphoma); (2) accordingly, it was unlikely that TG Therapeutics would be able to obtain U.S. Food and Drug Administration ("FDA") approval of the marginal zone lymphoma ("MZL") and follicular lymphoma ("FL") (the "Umbralisib MZL/FL NDA"), the rolling submission of a Biologics License Application ("BLA") to the FDA for Ublituximab in combination with Umbralisib (together, "U2"), as a treatment for patients with CLL (the "U2 BLA"), the supplemental New Drug Application ("sNDA") for Umbralisib to add an indication for CLL and small lymphocytic lymphoma ("SLL") in combination with Ublituximab (the "U2 sNDA"), or the Ublituximab as a treatment for patients with relapsing forms of multiple sclerosis ("RMS") (the "Ublituximab RMS BLA") in their current forms; (3) as a result, TG Therapeutics had significantly overstated Ublituximab and Umbralisib's clinical and/or commercial prospects; and (4) therefore, the Company's public statements were materially false and misleading at all relevant times. When the true details entered the market, the lawsuit claims that investors suffered damages. To join the TG Therapeutics class action, go to or call Phillip Kim, Esq. toll-free at 866-767-3653 or email [email protected] or [email protected] for information on the class action. No Class Has Been Certified. Until a class is certified, you are not represented by counsel unless you retain one. You may select counsel of your choice. You may also remain an absent class member and do nothing at this point. An investor's ability to share in any potential future recovery is not dependent upon serving as lead plaintiff. Follow us for updates on LinkedIn: , on Twitter: or on Facebook: . Attorney Advertising. Prior results do not guarantee a similar outcome. ------------------------------- Contact Information: Laurence Rosen, Esq. Phillip Kim, Esq. The Rosen Law Firm, P.A. 275 Madison Avenue, 40th Floor New York, NY 10016 Tel: (212) 686-1060 Toll Free: (866) 767-3653 Fax: (212) 202-3827 [email protected] pki[email protected] [email protected] SOURCE Rosen Law Firm, P.A.