Update on PSMC5 Foundation, Research, and the Next Event


Hello Everyone, 

It is hard to believe the summer is already over and we are already back to school and work.   We hope all of you had great summer.  We wanted to take a moment to give you a brief update on the PSMC5 Foundation activities over the past few months – a lot has been happening and we are excited to share both the research updates and the activities underway to grow the foundation, but first a quick refresh on who we are and why we created this foundation.

Quick Background

Our sons Ollie and Yoni share an de novo mutation in the PSMC5 gene.  This gene codes for a critical    component of the proteasome, a complex that degrades cellular proteins. When the proteasome does not work properly, many proteins accumulate in the cells. Since such proteins may regulate key cellular processes, this can result in cellular toxicity.  Both boys experience development delays and a number of medical complexities.  Over the past three years, we have been working closely with Dr. Alfred Goldberg and Dr. Galen Collins at Harvard Medical School and Dr. David Rubinsztein at Cambridge to understand how this mutation causes difficulties for cells, as a first step towards our desire to identify strategies that may enable amelioration of some of the its effects. We also believe that this research could benefit many others in the future, as the proteasome has been shown to have impacts on other neurological conditions that exhibit protein accumulation and cellular toxicity such as Alzheimers and Parkinsons.

Latest Research

The research team has been addressing the question of whether the mutation compromises proteasome function.  To address this, they depleted cells of PSMC5 and compared these cells either to non-depleted cells or to PSMC5-depleted cells to which they added back either normal or mutated PSMC5.  The experiments suggest that the mutation does indeed compromise proteasome function and this appears likely to be due to less PSMC5 activity. These strategies have also given us readouts of cellular stress and toxicity that we can use to start screening for approaches that may be able to reduce the cellular stresses caused by decreased PSMC5 activity.

For us non-technical laymen, this is both interesting and potentially practical for everybody.   The proteasome works closely in the body on a process called autophagy (on which Dr Rubinzstein is one of the world experts).  Like the proteasomal system, autophagy is a protein clearance mechanism and has gotten a lot of attention for its impact on aging.  Just as would a car that gets more regular maintenance and oil changes can go well beyond 100,000 miles, a body what efficiently clears cellular waste can last longer.   Given the desire to live longer, more research has focused on drugs and molecules that enhance autophagy, with a molecule called Rapamycin becoming a favorite in the biohacker and longevity community.  This is beyond scientific texts and popular in the spheres of Tim Ferris, Joe Rogan and Time Magazine.  

Our research team tested rapamycin, as well as some other similar compounds, and found that rapamycin was successful in suppressing apoptosis (cell death) that was due to the misfunctioning proteasome.  While this doesn’t mean we can start pumping Ollie and Yoni full of rapa, it does show we are moving beyond theory to expand into drug testing on animal models.  This is a huge step in the research process and a huge step towards finding a treatment that may help Ollie and Yoni in the future. 

Confidential:  Do not distribute

Next for the Research

The work done over the last 6 months has provided us with insights about the effects of compromised PSMC5 activity on cellular health and some of the deleterious processes that may be activated.   Along the way, we hope to also develop induced pluripotent stem cells models with the mutation that we can rapidly convert into human neurons and a mouse model that we can use to study the PSMC5 mutation at the organismal level.  The team aims to start developing the mouse model in the next 6 months. Our strategy is eventually to use these systems to test possible therapeutic strategies. 

We expect our research team to publish a paper in the coming months, which hopefully should attract more attention.

Winchester Wiffle Ball Tournament

Ok now for the fun stuff.  In the winter, we did a comedy fundraiser in New York City that was  successful and enjoyable.   For our next event, we are going to hold a Wiffle ball tournament and a special raffle to help raise funds for the next phase of research.    

Our goal for the fall fundraising efforts is to raise awareness and to create a fun, family event that we can host on an annual basis to continue to raise funds for the ongoing research.  We are planning a day of team work, family fun, some light competition, with great food and music.  We will have a dunk tank so volunteers are welcome for that!  The flyer is pasted below- we would love to see you there! 

We have also received some great donations to raffle at the Wiffle Fest including a SIGNED Tom Brady football (valued at $2000) and the Ultimate Red Sox Experience (valued at $5000-$7500). 

We have included details below if you would like to participate in the tournament and raffle: