The Salk approach, tested in a mouse model, points to cheaper and more effective treatments for humans
For most people with hemophilia B, whose bodies can’t properly form blood clots, constant injections to replenish their clotting factors are a way of life. But now, Salk researchers have demonstrated in mice that hemophilia B can be treated for life with one single injection containing disease-free liver cells that can produce their missing clotting factor. The finding, published in the journal Cell Reports on May 1, 2018, could drastically change what it means to be diagnosed with hemophilia B, and could pave the way toward similar treatments for other, related genetic disorders.
Hemophilia B is caused by defects in the gene for a protein called clotting factor IX (FIX). Hemophiliacs may make reduced amounts of the protein, or lack a functional version altogether, leading to life-threatening delays in blood clotting. Currently, patients are treated with injections—as often as a few times a week—containing FIX made in animal cells and then purified. But the approach is expensive, time-consuming and can become less effective over time.
Recently, Salk scientists developed a new approach, treating mice genetically engineered to have hemophilia B with strands of messenger RNA encoding the FIX gene. Like the standard treatment, however, this required repeat injections each time levels of the messenger RNA ran low. So the scientists wanted to try a more permanent approach: transplanting healthy liver cells, capable of producing FIX, into patients.
“The appeal of a cell-based approach is that you minimize the number of treatments that a patient needs,” says Suvasini Ramaswamy, a former Salk research associate in the Verma lab and first author of the new paper. “Rather than constant injections, you can do this in one shot.”
Since donor livers are often in short-supply, the researchers instead turned to stem-cell strategies to produce the healthy liver cells. They collected blood samples from two human patients with severe hemophilia B, who are unable to produce FIX. Then, in the lab, they reprogrammed the cells into induced pluripotent stem cells (iPSCs), which have the capability to turn into many other cell types, including liver. Using CRISPR/Cas9, a tool that can alter genes, they then repaired the mutations in each patient’s FIX gene. Finally, they coaxed those repaired cells to develop into liver precursor cells called hepatocyte-like cells (HLCs) and transplanted them into mice with hemophilia B.
Rather than perform surgery on hemophilic mice—a risky undertaking when their blood can’t always clot—the team transplanted the HLCs through the spleen to distribute the cells uniformly in the liver.
Not only did the new HLCs produce FIX, but they produced enough of the protein to allow the mice to form normal blood clots, and the cells continued to survive—and produce FIX—for at least a year after the transplantation.
In people with hemophilia, using their own cells to generate healthy HLCs, then transplanting them back into their bodies, could help avoid the immune complications that often accompany cell therapies. But more work is needed to translate the findings to the clinic.
“A lot of things have to happen before this can go into humans,” says Ramaswamy.
Already, she adds, the work demonstrates the value in combining stem-cell reprogramming and new gene-modifying approaches to treat genetic diseases.
The Latest on: Hemophilia B
via Google News
The Latest on: Hemophilia B
- Enable Injections inks development deals with pharma firms on November 13, 2018 at 7:06 am
The so-called enFuse device could be used to inject a large dose of medicine to combat anything from cancer to hemophilia. “En” stands for ... Enable had completed a first closing of a Series B round ... […]
- Global & US Gene Therapy Market Forecast to 2020 - Gene Therapy for Hemophilia B Offers Significant Opportunity - ResearchAndMarkets.com on November 9, 2018 at 5:27 am
DUBLIN--(BUSINESS WIRE)--The "Global & US Gene Therapy Market Forecast to 2020" report has been added to ResearchAndMarkets.com's offering. Gene therapy is one of the most widely researched fields ... […]
- New Data at ASH Showcase Bioverativ’s Commitment to Transforming Care for People with Hemophilia and Other Rare Blood Disorders on November 1, 2018 at 6:22 am
Of note, final study results from ASPIRE, Bioverativ and Sobi’s long-term extension study of ELOCTATE for hemophilia A, and B-YOND, the companies’ long-term extension study of ALPROLIX for hemophilia ... […]
- Bleeding score could help identify hemophilia on October 31, 2018 at 12:59 pm
Crystal/Wikimedia Commons/Creative Commons Attribution 2.0 Both hemophilia A and B patients had significantly higher bleeding scores as assessed by the ISTH-BAT (International Society on Thrombosis an... […]
- European Commission Approves IDELVION® --CSL Behring's Novel Hemophilia B Treatment with Up to 14-day Dosing Intervals on October 29, 2018 at 12:45 pm
PROLONG-9FP includes Phase I through Phase III open-label, multicenter studies evaluating the safety and efficacy of IDELVION in children and adults (ages 1 to 61 years) with hemophilia B (factor IX l... […]
- U.S. FDA expands approval of Roche hemophilia drug on October 4, 2018 at 1:08 pm
... condition as with hemophilia B. Reporting by John Miller in Zurich, Saumya Sibi Joseph and Ankur Banerjee in Bengaluru and Deena Beasley in Los Angeles; Editing by Shounak Dasgupta and Bill Berkro... […]
- With success in gene therapy trials, hemophilia may no longer be a 'lifelong thing' on September 6, 2018 at 9:06 pm
A handful of biotech companies are rushing to get their gene therapies to market. Spark, with gene therapy for hemophilia B, and BioMarin, with a treatment for hemophilia A, are starting final-phase c... […]
- Spark's Gene Therapy For Hemophilia B Looks To Change Up The Game on September 2, 2018 at 12:01 am
Spark Therapeutics posts positive phase 1/2 results treating patients with Hemophilia B using SPK-9001. Pfizer is expected to lead the rest of the development for the Hemophilia B candidate SPK-9001 b... […]
- uniQure Makes Substantial Progress Towards A Large Hemophilia B Market on August 27, 2018 at 10:32 am
uniQure announced that it dosed the first patient for its phase 2b dose confirmation study treating patients with Hemophilia B using the more advanced AMT-061 with the FIX padua variant. uniQure is al... […]
via Bing News