Animal results may pave way to treating rare mitochondrial diseases in children

May 19, 2011 in Medical research

A human drug that both prevents and cures kidney failure in mice sheds light on disabling human mitochondrial disorders, and may represent a potential treatment in people with such illnesses.

"There are no effective cures for mitochondrial diseases, even in animals," said study leader Marni J. Falk, M.D., who cares for children in the Mitochondrial-Genetics Disease Clinic at The Children's Hospital of Philadelphia. "So these striking results in mice may suggest a novel therapy of direct relevance for humans."

Falk and colleagues published their study online May 5 in the journal EMBO Molecular Medicine.

Mitochondria are tiny structures that operate as powerhouses within human and animal cells, generating energy from food. As such, they are fundamental to life. Failures of proper impair a wide range of organ systems.

Individually, mitochondrial diseases are very rare. However, because there are hundreds of these disorders, they collectively have a broad impact, affecting at least 1 in 5,000 people, and possibly more. Malfunctioning mitochondria also contribute to complex disorders, including diabetes, epilepsy, Alzheimer's disease and .

The current study focused on an inherited genetic deficiency that prevents the production of coenzyme Q, a critical antioxidant and component of the energy-generating respiratory chain. In humans and in the used to model this disease, the deficiency results in fatal . The current treatment, which consists of providing regular supplements of the missing enzyme product, , is often ineffective.

Falk's team fed the mutant mice probucol, an oral drug formerly used to treat people with (since replaced for that purpose by ). The drug prevented the mice from developing , and also reversed kidney disease in mice that had already developed it. It also raised the levels of coenzyme Q10 within the animals' tissues and corrected signaling abnormalities.

"This drug showed remarkable benefits in the mice, especially when compared to directly feeding the mice supplements of the missing co-factor—coenzyme Q10," said Falk. "If this approach can be safely translated to humans, we may have a more effective treatment for mitochondrial disease than anything currently being used."

Primary coenzyme Q deficiency is vanishingly rare in humans—only a few dozen people are known to have the disease. However, said Falk, the disease is representative of a more common group of inherited, hard-to-treat mitochondrial diseases called respiratory chain (RC) defects.

RC defects share a common cellular failure to properly consume oxygen for the purposes of generating energy. Such defects, caused by a wide range of genetic disorders that affect mitochondria, constitute a common culprit in human mitochondrial disease. "If using probucol or a similar drug can benefit patients with defects in the respiratory chain, this could be a significant advance in treating ," said Falk.

At the very least, added Falk, the current study increases basic understanding of the biology of mitochondrial disease. She noted that continuing research building on her team's findings may set the stage for eventual clinical trials using this approach.

More information: "Probucol ameliorates renal and metabolic sequelae of primary CoQ deficiency in Pdss2 mutant mice," EMBO Molecular Medicine, published online May 5, 2011. doi: 10.1002/emmm.201100149

Provided by Children's Hospital of Philadelphia search and more info website

not rated yet  

Rank not rated yet
Relevant PhysicsForums posts

More news stories

Study suggests new source of kidneys for transplant

Nearly 20 percent of kidneys that are recovered from deceased donors in the U.S. are refused for transplant due to factors ranging from scarring in small blood vessels of the kidney's filtering units to the organ going too ...

Medical research created 13 hours ago | popularity 5 / 5 (2) | comments 0 | with audio podcast

Discovery of circadian clock in mice hair reveals period of time when damage from radiotherapy can be quickly repaired

Discovering that mouse hair has a circadian clock - a 24-hour cycle of growth followed by restorative repair - researchers suspect that hair loss in humans from toxic cancer radiotherapy and chemotherapy ...

Medical research created 14 hours ago | popularity 5 / 5 (2) | comments 1 | with audio podcast

Do salamanders hold the solution to regeneration?

Salamanders' immune systems are key to their remarkable ability to regrow limbs, and could also underpin their ability to regenerate spinal cords, brain tissue and even parts of their hearts, scientists have ...

Medical research created 15 hours ago | popularity 4.9 / 5 (7) | comments 2 | with audio podcast

New study finds blind people have the potential to use their 'inner bat' to locate objects

New research from the University of Southampton has shown that blind and visually impaired people have the potential to use echolocation, similar to that used by bats and dolphins, to determine the location of an object.

Medical research created 17 hours ago | popularity not rated yet | comments 1 | with audio podcast

Germ-fighting vaccine system makes great strides in delivery

A novel vaccine study from South Dakota State University (SDSU) will headline the groundbreaking research that will be unveiled at the American Association of Pharmaceutical Scientists' (AAPS) National Biotechnology Conference ...

Medical research created 18 hours ago | popularity not rated yet | comments 0


Holding drivers' attention

Each day, an average of nine people are killed in the United States and more than 1,000 injured by drivers doing something other than driving.

Genetic predictors of postpartum depression uncovered

Johns Hopkins researchers say they have discovered specific chemical alterations in two genes that, when present during pregnancy, reliably predict whether a woman will develop postpartum depression.

Nobel laureate plays down flu pandemic scaremongering

A Nobel prize-winning scientist Tuesday played down "shock-horror scenarios" that a new virus strain will emerge with the potential to kill millions of people.

Study puts Huntington's disease trials on TRACK

(Medical Xpress)—A three-year multinational study has tracked and detailed the progression of Huntington's disease (HD), predicting clinical decline in people carrying the HD gene more than 10 years before ...

Child maltreatment increases risk of adult obesity

Children who have suffered maltreatment are 36% more likely to be obese in adulthood compared to non-maltreated children, according to a new study by King's College London. The authors estimate that the prevention or effective ...

New immune system discovered

(Medical Xpress)—A research team, led by Jeremy Barr, a biology post-doctoral fellow, unveils a new immune system that protects humans and animals from infection.