Wolozin Lab Shows that the Stress Granule Pathway Contributes to Alzheimer's Disease

CAMBRIDGE, MA, May 5, 2016 /PRNewswire/ - Dr. Benjamin Wolozin’s laboratory has shown that the pathway leading to neurodegeneration in Alzheimer’s disease (AD) is similar to the stress granule pathway implicated in amyotrophic lateral sclerosis (ALS). This work opens up AD to the innovative drug discovery approaches pioneered by Aquinnah Pharmaceuticals Inc. 

The findings, published today in a leading journal, Cell Reports, focuses on the tau protein, whose abnormal aggregation (clumping) has long been known to drive the nerve damage in AD. New research shows that the tau protein directs the formation of stress granules, which are molecular complexes that allow nerve cells to adapt to stresses, such as injury. The tau-stress granule complex is usually short lived, but in the setting of chronic stress, tau persistently forms into a cluster, leading to the degeneration of nerve cells seen in AD. 

Dr. Wolozin, MD, PhD, who is Chief Scientific Officer of Aquinnah Pharmaceuticals Inc., and a professor at Boston University School of Medicine explains, “Scientists have known for a long time that during disease, tau protein gets modified, changes its location in nerve cells, and then aggregates.” In healthy nerve cells, tau resides in a part of the nerve cell termed the axon, the long, slender part of the cell that carries electrical impulses away from the neuron’s body. Wolozin’s group showed that moving tau from the axon to the nerve cell body helps the nerve cells respond to stress (such as injury). “The nerve cells do this in order to stimulate the formation of stress granules, which help the cell to adapt under stressful conditions. Stress granules instruct the cell to divert energy toward making protective proteins and away from making specialized proteins, which are less necessary during stress.” 

“Surprisingly,” says Wolozin, “the association of tau with stress granules also caused tau to cluster. Most stresses are short term, resolve quickly and are therefore not a problem. But some stresses are chronic, such as vascular disease or the accumulation of beta-amyloid - a protein that accumulates outside the neuron in Alzheimer’s disease.” Chronic stress leads to excessive, persistent accumulation of stress granules containing aggregated tau, which ultimately damages nerve cells, causing degeneration.” 

According to Wolozin, with this finding comes hope. His team found that reducing the amount of one of the key stress granule proteins, TIA1, prevented tau aggregation and nerve cell degeneration. “While still in its early stages, this work points to entirely new approach that is now being pursued to treat Alzheimer’s disease.”. The BrightFocus Foundation, the Alzheimer Association, the Cure Alzheimer’s Fund and the National Institute of Health provided funding for this work. 

About Aquinnah Pharmaceuticals

Aquinnah Pharmaceuticals is using newly discovered brain pathology to design innovative therapies to slow the progression of ALS, AD and other neurodegenerative diseases. Aquinnah builds on the groundbreaking work of co-founder Benjamin Wolozin, M.D., Ph.D., Professor of Pharmacology, Neurology and the Program in Neuroscience at Boston University, who has led the discovery of disease-linked protein aggregation in neurologic diseases. Additional information about Aquinnah is available through its corporate website, www.aquinnahpharmaceuticals.com

Aquinnah Contacts – news@aquinnahpharma.com

Aquinnah Pharmaceuticals Presents New Therapeutic Approaches For ALS, in an ALS Association Webinar

 

CAMBRIDGE, MA, April 27, 2016 /PRNewswire/ - Aquinnah Pharmaceuticals announced that it will present an ALS Association hosted Research Webinar, today at 4 PM EDT. Dr. Glenn Larsen, President & CEO, and Dr. Benjamin Wolozin, CSO, will discuss their work in a presentation entitled “New Therapeutic Approaches for ALS Based on RNA Binding Proteins”. 

Aquinnah’s technology platform represents an innovative approach that targets pathological protein complexes found in the brain of the majority of patients with ALS. The accumulation of these disease-linked protein complexes are believed to drive the progression of ALS. Aquinnah has designed its newly identified compounds to slow or reverse the progression of ALS by attacking and breaking down these protein complexes, with the goal of swiftly moving a new and effective class of ALS drugs into clinical development. 

Currently there is no cure or effective treatment for slowing the progression of ALS, a lethal neurodegenerative disease that quickly stifles nerve cell function, leading to loss of muscle control throughout the body. ALS can progress rapidly, with more than half of newly diagnosed patients not surviving beyond three years. 

In 2015, Aquinnah received grants from four peer-reviewed organizations, including funding from the ALS Association (ALSA), US National Institute of Health – National Institute of Neurological Disorders and Stroke, and the Massachusetts Life Sciences Center. In addition, Aquinnah also received an investment of $5 Million from Takeda Pharmaceuticals. 

“We are pleased to report on our progress enabled by support from the ALSA”, said Glenn Larsen, Ph.D., President, CEO and co-founder of Aquinnah. “Our research and development efforts are progressing well and we expect that our approach will potentially treat the majority of patients with ALS, not just a small subset of patients with the disease. “Aquinnah’s approach is unique by integrating human genetic, human pathology and cellular biology R&D expertise, towards the development of a new therapeutic drug”, said Ben Wolozin, M.D., Ph.D., and co-founder of Aquinnah. “Our approach has unveiled novel opportunities for therapeutic intervention that are believed to be able to halt the progression, or even reduce aspects of neurodegenerative diseases that were previously thought to be irreversible. We expect these approaches to extend beyond ALS, including other neurodegenerative diseases such as Alzheimer’s disease and Fronto-Temporal Dementia (FTD), where similar pathologic proteins accumulate.” 

Additional information regarding Aquinnah Pharmaceuticals and Registration for the ALSA Webinar can be found at https://alsa.webex.com/alsa/ldr.php?RCID=c1a8012dfcfaa589e492b475ed265f58

About Aquinnah Pharmaceuticals

Aquinnah Pharmaceuticals is using newly discovered brain pathology to design innovative therapies to slow the progression of ALS and other neurodegenerative diseases. Aquinnah builds on the groundbreaking work of co- founder Benjamin Wolozin, M.D., Ph.D., Professor of Pharmacology, Neurology and the Program in Neuroscience at Boston University, who has led the discovery of disease-linked protein aggregation in neurologic diseases. Additional information about Aquinnah is available through its corporate website, www.aquinnahpharmaceuticals.com

Aquinnah Contacts – news@aquinnahpharma.com

About The ALS Association

The ALS Association is a national non-profit organization fighting Lou Gehrig’s disease on every front. By leading the way in global research, providing assistance for people with ALS through a nationwide network of chapters, coordinating multidisciplinary care through certified clinical care centers, and fostering government partnerships. The Association builds hope and enhances quality of life while aggressively searching for new treatments and a cure. For more information about the ALS Association, visit our website at www.alsa.org

Aquinnah Pharmaceuticals Receives $5 Million Investment from Takeda Pharmaceuticals To Advance New Therapies in ALS

CAMBRIDGE, MA, December 21, 2015 /PRNewswire/ - Aquinnah Pharmaceuticals announced today that it has received a $5 Million investment from Takeda Pharmaceutical Company, Limited, in it’s first private equity financing. The company has assembled a world- class team of drug developers and an exceptional Scientific Advisory Board in the fields of Amyotrophic Lateral Sclerosis (ALS), protein and RNA regulation, and neurodegenerative diseases. 

Aquinnah’s technology platform represents an innovative approach that targets pathological protein complexes found in the brain of the majority of patients with ALS. The accumulation of these disease-linked protein complexes are believed to drive the progression of ALS. Aquinnah has designed its newly identified compounds to slow or reverse the progression of ALS by attacking and breaking down these protein complexes, with the goal of swiftly moving a new and effective class of ALS drugs into clinical development. 

Currently there is no cure or effective treatment for slowing the progression of ALS, a lethal neurodegenerative disease that quickly stifles nerve cell function, leading to loss of muscle control throughout the body. ALS can progress rapidly, with more than half of newly diagnosed patients not surviving beyond three years. 

“We are pleased to have received this strategic investment from Takeda”, said Glenn Larsen, Ph.D., President and CEO of Aquinnah. “This funding adds further momentum to the numerous peer reviewed grants that we have received and will accelerate our program toward clinical development of new drugs for ALS and other neurodegenerative diseases”. 

“Our investment in Aquinnah Pharmaceuticals reflects Takeda’s commitment to supporting innovative research in areas of high unmet medical need,” said Dr. Ceri Davies, Head of Takeda Central Nervous System Drug Discovery. “We believe that Aquinnah’s program is among the most promising new approaches to treating neurodegenerative diseases.” 

About Aquinnah Pharmaceuticals 

Aquinnah Pharmaceuticals is using newly discovered brain pathology to design innovative therapies to slow the progression of ALS and other neurodegenerative diseases. Aquinnah builds on the groundbreaking work of co-founder Benjamin Wolozin, M.D., Ph.D., who has led the discovery of disease-linked protein aggregation in neurologic diseases. Additional information about Aquinnah is available through its corporate website, www.aquinnahpharmaceuticals.com 

Aquinnah Contacts – news@aquinnahpharma.com