Ice Bucket Dollars at Work: Ubiquilin-2 (UBQLN2) is Linked to Cellular Stress Granules

We recently sat down with Dr. Carlos Castañeda, assistant professor of biology and chemistry at Syracuse University. Thanks to funding from the ALS Ice Bucket Challenge, The ALS Association has funded Dr. Castañeda twice through our global research program, which supported this work.

Dr. Castañeda talked with us about the important findings in his recently published paper in Molecular Cell. His research explores cell degradation pathways with a focus on ubiquilin-2 (UBQLN2), a shuttle protein associated with ALS. Importantly, this work further links dysregulation of protein quality control pathways to ALS disease states.

Continue reading Ice Bucket Dollars at Work: Ubiquilin-2 (UBQLN2) is Linked to Cellular Stress Granules

Guest Post: What I Learned from Stephen Hawking

By Dr. Richard Bedlack

I woke up this morning to the terrible news that Stephen Hawking died. While I never met the man, and didn’t really understand all he was saying about black holes, I learned a lot from him about what is possible for people with ALS.

At his diagnosis, Hawking was reportedly told that he would only live a few years and that there was nothing that could be done for him.

He beat his prognosis by many decades. While he appeared to decline a lot in the beginning of his illness, his progression seemed to slow, or even stop in later years. His course opened my eyes to the idea that there can be marked variability between people with ALS, and even within a given patient at different times.

Continue reading Guest Post: What I Learned from Stephen Hawking

Remembering Stephen Hawking, Who Inspired the ALS Community and the World

The ALS Association mourns the loss of Dr. Stephen Hawking and commemorates his life and legacy.

Hawking, a renowned physicist and best-selling author who famously studied black holes and whose life was depicted in the 2014 film The Theory of Everything, was diagnosed with ALS, also known as Lou Gehrig’s Disease, in 1963. The average life expectancy of person living with ALS is approximately two to five years after diagnosis and only 10 percent of people survive for more than 10 years.

He served as an inspiration for many in all walks of life, including people living with ALS around the world.

“Be curious, and however difficult life may seem, there is always something you can do, and succeed at. It matters that you don’t just give up,” Hawking once said.

ALS Association Board of Trustees Chair Stephen Winthrop spoke of Hawking’s impact.

“Most people describe ALS as a disease that, bit by bit, robs a patient’s ability to move and function. But Stephen Hawking has inspired me to focus on what I can do, rather than what my body can no longer do,” Winthrop said.

Ice Bucket Dollars at Work: Microglia Shown Neuroprotective in ALS TDP-43 Mice

Research funded with donations from the ALS Ice Bucket Challenge recently uncovered evidence that promoting an increase in a specific immune cell in the brain and spinal cord of a mouse with ALS was associated with increased motor function, pointing to a potential treatment in the future.

During ALS disease, motor neurons degenerate and eventually die, resulting in a loss of the connection to muscles, which in turn weaken and eventually paralyze. Several studies have shown that microglia, which are a type of immune cell in the brain and spinal cord, increase the severity of neurodegeneration in ALS. Others have shown that microglia can contribute to maintaining the health of neurons.

Drs. Virginia Lee, Krista Spiller, and colleagues from the Perelman School of Medicine at the University of Pennsylvania in Philadelphia set out to understand how microglia function in the brain and spinal cord to either protect against or contribute to neurodegeneration.

The ALS Association currently funds Dr. Spiller under our Investigator-Initiated Starter Grant program using donations from the ALS Ice Bucket Challenge. Their paper was published in the February 20 issue of Nature Neuroscience journal.

They found that microglia can play a protective role in the brain and spinal cord in a TDP-43 mouse model. This suggests that encouraging healthy microglia to proliferate in cells could translate into a potential ALS therapy in the future.

Continue reading Ice Bucket Dollars at Work: Microglia Shown Neuroprotective in ALS TDP-43 Mice

Guest Post: Patient Voices Matter

This guest post is from Shelly Hoover, EdD, a member of the Patient & Caregiver Advisory Committee, and does not necessarily reflect the opinions of the Association staff, its Board of Trustees, or its chapters.

By guest blogger Shelly Hoover

Patient voices matter, yet the collective ALS patient community has been too patient and too quiet for too long.

The ALS Association led an unprecedented effort to develop an FDA Guidance Document for Industry. Here’s a quote from the introduction:

“In February of 2015, The ALS Association launched this effort to develop the first-ever community-driven drug development guidance for ALS with funding from the ALS Ice Bucket Challenge, bringing together over 100 participants including people living with ALS, caregivers, researchers, clinicians, and industry experts from across the world to contribute their expertise and experience. In parallel with this effort, a committee was formed to update the ALS clinical trial guidelines that were developed more than 15 years ago. The guidance and guidelines have different audiences and different goals, yet are meant to be consistent. This guidance is intended to represent the Agency’s interpretation of, or policy on, evaluating new ALS therapies for approval in order to assist industry in navigating the regulatory process. The clinical trial guidelines incorporate stakeholder views across all phases of drug development, from preclinical to market approval, and serve as “best practices” for clinical trial design and are used by researchers and industry to provide structure and direction for the design and conduct of clinical trials in ALS. The goal of clinical trial guidelines is to lead to more effective and efficient trials, but they do not directly impact the FDA regulatory process.”

This guidance and the subsequent FDA document ALS: Developing Drugs for Treatment; Draft Guidance for Industry, are conservative and uphold the FDA’s gold standards for drug trial design and approval. That is great news for patients who will be diagnosed decades from now. Patients who are living with ALS today will not benefit in any significant way. As a person living with ALS, I find this conservative approach unacceptable.

I applaud The ALS Association ’s efforts. However, as a member of the patient advisory committee, I feel the patient voice was drowned out by louder voices in the development of the FDA Guidance. Read the last sentence in the introductory paragraph (bold emphasis mine). Are minor tweaks in trial design going to get potential treatments to patients now? And, why aren’t we pushing for changes to the archaic FDA regulatory process?

Here are two changes that the patient community can demand today:

  1.  Use historical controls instead of placebos until we have a widely effective treatment.
  2. Treatments in Phase 2 must be made available all patients. This will require changes to the FDA Expanded Access Program that currently does not incentivise nor protect drug manufacturers

You can make a difference by forming your own opinion and leaving a public comment here. Please do it today.

Let me be perfectly clear — this is not an ALS Association problem. The Association has multiple stakeholders, and the patient community played nice and our quiet voice got buried in the last pages of the The ALS Association Guidance Document (see Appendix C, of ALSA’s document). This is not an FDA problem. The FDA is upholding their gold standards of drug safety and approval. Why would they change?

This problem lies squarely on the shoulders of the patient community. We have the responsibility to speak out, speak loudly, and speak now. We need 1,000 public comments to get the FDA’s attention (101 comments have been submitted at the time of this writing). Then,  we must demand changes and do whatever it takes to save our own lives. If we don’t act now, we will die waiting for someone else to act for us.

About the Author

Shelly Hoover, EdD was diagnosed with ALS five years ago at age 47. She is an ALS Advocate, retired public school administrator, and US Navy Veteran. Shelly lives with her husband, Steve, in Northern California.

The ALS Association, Huntington’s Disease Society of America, and Teva Pharmaceuticals Launch Teva CNS Target Identification Challenge

Central nervous system (CNS) disorders afflict approximately 300 million people worldwide. They often span many years and are severely debilitating. And, in addition to the personal cost to patients and families, the economic burden reaches an estimated $1.5 trillion annually in the U.S.

Significant investment in the development of new therapies must be made to improve outcomes for people suffering from CNS disorders. Unraveling the disease pathways contributing to these disorders and identifying novel molecular targets for drug intervention are essential steps toward developing new treatment avenues.

Continue reading The ALS Association, Huntington’s Disease Society of America, and Teva Pharmaceuticals Launch Teva CNS Target Identification Challenge

ALS Reproducible Antibody Platform is Created to Ensure Highest-Quality Antibodies to the ALS Community

The ALS Association, in partnership with the Motor Neurone Disease Association (MND Association), and the ALS Society of Canada, have come together to support the ALS Reproducible Antibody Platform (ALS-RAP) with a $600,000 grant to create an open-access pipeline to validate antibody research. ALS-RAP will provide the ALS research community with the highest quality reliable, renewable antibodies for ALS genes to galvanize and enable a faster and even more efficient development of therapies to address the ALS challenge, globally.

“The ALS Association is delighted to fund this exciting initiative and believe it will be an extremely valuable open resource for researchers across the globe,” said Dr. Lucie Bruijn, chief scientist at The ALS Association

Continue reading ALS Reproducible Antibody Platform is Created to Ensure Highest-Quality Antibodies to the ALS Community