Transplanted hematopoietic stem cells reverse damage caused by neuro-muscular disorder

Researchers at University of California San Diego School of Medicine report that a single infusion of wildtype hematopoietic stem and progenitor cells (HSPCs) into a mouse model of Friedreich's ataxia (FA) measurably halted cellular damage caused by the degenerative disease. The findings, published online in the October 25 issue of Science Translational Medicine, suggest a potential therapeutic approach for a disease that currently is considered incurable.

Friedreich's ataxia is an inherited, degenerative neuromuscular disorder that initially impairs motor function, such as gait and coordination, but can lead to scoliosis, heart disease, vision loss and diabetes. Cognitive function is not affected. The disease is progressively debilitating, and ultimately requires full-time use of a wheelchair. One in 50,000 Americans has FA.

FA is caused by reduced expression of a mitochondrial protein called frataxin (FXN) due to a two mutated or abnormal copies of the FXN gene. In their study, Stephanie Cherqui, PhD, associate professor in the UC San Diego School of Medicine Department of Pediatrics, and colleagues used a transgenic mouse model that expresses two mutant human FXN transgenes, and exhibits the resulting progressive neurological degeneration and muscle weakness.

Human hematopoietic stem and progenitor cells (HSPCs), derived from bone marrow, have become a primary vehicle for efforts to replace or regenerate cells destroyed by a variety of diseases. Previous research by Cherqui and colleagues had shown that transplanting wildtype or normal mouse HSPCs resulted in long-term kidney, eye and thyroid preservation in a mouse model of cystinosis, another genetic disorder.

In this study, Cherqui's team transplanted wildtype HSPCs into an FA mouse model, reporting that the HSPCs engrafted and soon differentiated into macrophages in key regions of the mice's brain and spinal cord where they appeared to transfer wildtype FXN into deficient neurons and muscle cells.

"Transplantation of wildtype mouse HSPCs essentially rescued FA-impacted cells," said Cherqui, "Frataxin expression was restored. Mitochondrial function in the brains of the transgenic mice normalized, as did in the heart. There was also decreased skeletal muscle atrophy."

The scientists note that the mouse model is not perfect mirror of human FA. Disease progression is somewhat different and the precise pathology in mice is not fully known. However, Cherqui said the findings are encouraging and point toward a potential treatment for a disease that currently has none.

Celine J Rocca, Spencer M Goodman, Jennifer N Dulin, Joseph H Haquang, Ilya Gertsman, Jordan Blondelle, Janell LM Smith, Charles J Heyser, Stephanie Cherqui.
Transplantation of wild-type mouse hematopoietic stem and progenitor cells ameliorates deficits in a mouse model of Friedreich's ataxia.
Science Translational Medicine, Vol. 9, Issue 413, eaaj2347. doi: 10.1126/scitranslmed.aaj2347

Most Popular Now

A great place to do great things: Developing game-…

Science has spoken: Abbott (NYSE: ABT) is, again, among the best science-based companies to work for in the world. For the 14th year, the journal Science today recognized...

FDA accepts regulatory submission for Lynparza in …

AstraZeneca and Merck & Co., Inc., (Merck: known as MSD outside the US and Canada) today announced that the US Food and Drug Administration (FDA) has accepted and granted...

Alzheimer's disease might be a 'whole body' proble…

Alzheimer's disease, the leading cause of dementia, has long been assumed to originate in the brain. But research from the University of British Columbia and Chinese scie...

Cancer cells destroyed with dinosaur extinction me…

Cancer cells can be targeted and destroyed with the metal from the asteroid that caused the extinction of the dinosaurs, according to new research by an international col...

Novartis confirms leadership in multiple sclerosis…

Novartis today announced it will present 54 scientific abstracts from across its multiple sclerosis (MS) research portfolio at the 7th Joint European and Americas Committ...

Three of the most deadly cancers get critical fund…

Immunotherapy for leukemia patients has been nothing short of a miracle. Now scientists hope to use that science and other forms of gene therapy to tackle three of the de...

Transplanted hematopoietic stem cells reverse dama…

Researchers at University of California San Diego School of Medicine report that a single infusion of wildtype hematopoietic stem and progenitor cells (HSPCs) into a mous...

Amgen and Novartis announce expanded collaboration…

Amgen (NASDAQ:AMGN) and Novartis announced an expanded collaboration with the Banner Alzheimer's Institute (BAI) to initiate a new trial - the Alzheimer's Prevention Init...

Scientists find where HIV 'hides' to evade detecti…

In a decades-long game of hide and seek, scientists from Sydney's Westmead Institute for Medical Research have confirmed for the very first time the specific immune memor...

'Precision Medicine' may not always be so precise

Precision Medicine in oncology, where genetic testing is used to determine the best drugs to treat cancer patients, is not always so precise when applied to some of the w...

Novartis announces the planned acquisition of Adva…

Novartis announced today, that it has entered a memorandum of understanding with Advanced Accelerator Applications (AAA) under which Novartis intends to commence a tender...

China's out of control 'silent killer' affects one…

More than one-third of adults in China have high blood pressure - often dubbed the "silent killer" for its lack of symptoms - but only about one in 20 have the condition ...

Pharmaceutical Companies

[ A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Z ]