Dear KD Family,
In this time of the Coronavirus pandemic, we at the KDA would like to urge extra caution for those with Kennedy’s Disease. The Coronavirus can cause lower respiratory congestion, which is difficult for some people with KD to deal with, since we have trouble producing productive coughs. If you are someone with respiratory difficulties, or are age 60 or older, we would include you in the higher risk population.
Please adhere to the recommendations by the Center for Disease Control on ways to prevent exposure to the Coronavirus, as this is your best defense. The CDC tells us that: The virus is thought to spread mainly from person-to-person (within about 6 feet) through respiratory droplets produced when an infected person coughs or sneezes. These droplets can land in the mouths or noses of people who are nearby or possibly be inhaled into the lungs.
It is recommended that you avoid close contact with people and large gatherings. Also, wash your hands frequently and avoid touching your face. To see more in depth information, click on the link to see the information the CDC has provided to help prevent infection.
In the interest of learning from your experience, we ask that you or a care provider contact the KDA if you test positive for the Coronavirus. Continue to live your lives, but do so in a way that keeps you and your loved ones at minimal risk. We wish you health and freedom from fear.
The Board of Directors of the KDA
Thank you to Louise Goforth who is retiring from the KDA board. For several years now, Louise has lead our fundraising efforts and with her leadership has brought our ability to fund research amazing new heights. Multiple $50,000 grants given to researchers can be attributed directly to her efforts to mobilize the KD community. Fortunately, she will continue to work doing the Texas Golf Scramble which has been the biggest fundraising effort in the history of the KDA. Louise, your steady leadership, positive outlook and joyful disposition will be missed on the board of directors. On behalf of the entire KD community, we thank you.
The NIH-funded Rare Diseases Clinical Research Network is conducting an online research survey to understand the impacts of Covid-19 on the rare disease community.
To better understand how individuals with rare diseases and their families are impacted by the COVID-19 pandemic, the NIH-funded Rare Diseases Clinical Research Network developed a twenty minute online research survey from home. This survey will provide an opportunity for rare disease patients and caregivers to share their experiences and help researchers learn more about community needs during a time of crisis. Learn more about this survey by clicking here.
Arginine is a disease modifier for polyQ disease models that stabilizes polyQ protein conformation
In this study, we identified arginine as a potent polyQ aggregation inhibitor that acts by inhibiting the formation of misfolded and oligomeric toxic protein species before the formation of insoluble aggregates. We also confirmed its therapeutic effects on neurological symptoms and protein aggregation pathology using two different animal models of polyQ diseases. In addition, we showed that arginine may exert a therapeutic effect on the dendritic arborization of the Purkinje cell in the cerebellum. To read the article, click here.
Muscle BDNF: A Potential Therapeutic Target for Kennedy’s Disease
Novel to this study, the authors developed a 97Q mouse with Cre-dependent overexpression of BDNF (97Q/BDNF) specifically in muscle. This resulted in significant increases in muscle-specific BDNF expression by 150-fold in the fast-twitch tibialis anterior (TA) and 45-fold in the slow-twitch soleus. The hang test, used to determine disease progression, demonstrates neuromuscular impairment and motor coordination in mouse models by measuring how long a mouse can hold their bodyweight using an overhanging bar. In the current study, disease onset was defined as a hang time < 120 seconds for two consecutive days and a hang-time < 30 seconds represented disease end-stage. Overexpression of BDNF was found to significantly increase time to disease onset, endstage and further, doubled survival time. To read the article, click here.
Cell-Clearing Systems Bridging Repeat Expansion Proteotoxicity and Neuromuscular Junction Alterations in ALS and SBMA
The coordinated activities of autophagy and the ubiquitin proteasome system (UPS) are key to preventing the aggregation and toxicity of misfold-prone proteins which manifest in a number of neurodegenerative disorders. These include proteins which are encoded by genes containing nucleotide repeat expansions. In the present review we focus on the overlapping role of autophagy and the UPS in repeat expansion proteotoxicity associated with chromosome 9 open reading frame 72 (C9ORF72) and androgen receptor (AR) genes, which are implicated in two motor neuron disorders, amyotrophic lateral sclerosis (ALS) and spinal-bulbar muscular atrophy (SBMA), respectively. At baseline, both C9ORF72 and AR regulate autophagy, while their aberrantly-expanded isoforms may lead to a failure in both autophagy and the UPS, further promoting protein aggregation and toxicity within motor neurons and skeletal muscles. Besides proteotoxicity, autophagy and UPS alterations are also implicated in neuromuscular junction (NMJ) alterations, which occur early in both ALS and SBMA. In fact, autophagy and the UPS intermingle with endocytic/secretory pathways to regulate axonal homeostasis and neurotransmission by interacting with key proteins which operate at the NMJ, such as agrin, acetylcholine receptors (AChRs), and adrenergic beta2 receptors (B2-ARs). Thus, alterations of autophagy and the UPS configure as a common hallmark in both ALS and SBMA disease progression. To read the article, click here.