KDA Conference 2020 Goes Virtual!

Conference Dates: Wednesday, October 14th & Thursday, October 15th. In the face of the global pandemic, the KDA has decided to move this year's 2020 KDA conference ONLINE!  This years conference will be 2 half-days, mornings in the U.S. and afternoons in the U.K. This is a joint effort with the UK and the theme is "Moving Forward Together." More specific information on the agenda and sign-up will be coming out shortly, meanwhile, mark your calendars. These are challenging times. And though we may have to stay home for this conference, we can still connect and continue the fight for a cure!

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.

Wide range of reduced penetrance alleles in spinal and bulbar muscular atrophy: a model based approach

Our analysis reveals an unexpectedly high frequency of expanded SBMA-associated alleles, with (CAG)n ≥35 present in 107/100,000 and (CAG)n ≥38 present in 27/100,000 of the general population. We argue against the cut-off model for the penetrance of SBMA and suggest that penetrance gradually increases from 35 to approximately 46 repeats, above which it reaches a plateau approaching maximum value. Therefore, asymptomatic men of the general population with no/ unknown SBMA family history are free of risk when carrying (CAG)n ≤34, are at intermediate but increasing risk for developing SBMA (with greater risk for longer alleles) when carrying (CAG)n ≈35–46 and have close to 100% risk of developing the disease when carrying (CAG)n ≥47. To read the article, click here.

Sonic Hedgehog-Gli1 Signaling and Cellular Retinoic Acid Binding Protein 1 Gene Regulation in Motor Neuron Differentiation and Diseases

We employed the same strategy to engineer healthy vs. degenerated MN1 cells to model SBMA neurons [22]. MN1 cells containing AR-24Q (control) remain healthy, whereas MN1 cells containing the diseased version, AR-65Q, become degenerated in cultures As shown in Figure 2b, the diseased SBMA/MN1 neurons, AR-65Q, also have a dramatically reduced CRABP1 level, as compared to the healthy control, AR-24Q. These results, in two motor neuron disease models, consistently show that Crabp1 gene activity is positively correlated with a healthy state in motor neurons, whereas down regulation of the Crabp1 gene is correlated with degeneration in motor neurons, such as those in ALS and SBMA. To read the article, click 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.