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
- What We Learned in 2018: Health and Medicine on December 20, 2018 at 2:06 am
Warner III, Memorial Sloan Kettering’s board chairman; Dr. José Baselga, its former chief medical officer; and Dr. Craig B. Thompson, its chief executive ... have lived with hemophilia most of their l... […]
- Famous People Affected by Hemophilia on December 18, 2018 at 12:57 pm
A person with hemophilia A, the most common type, lacks clotting factor 8, while a person with hemophilia B lacks clotting factor 9. Most often, hemophilia is a congenital disease, meaning the person ... […]
- Catalyst Biosciences Hosts Research & Development Day Focused on Factor VIIa and Factor IX Hemophilia Programs on December 18, 2018 at 9:07 am
In the Phase 2 portion of the Phase 2/3 trial of MarzAA for the treatment of hemophilia A or B with inhibitors: • Catalyst plans to conduct a global Phase 3 clinical study assessing reductions ... […]
- Living with Hemophilia on December 17, 2018 at 12:46 pm
But the videos they’re making are not just for the entertainment of others. They’re being used to raise awareness about hemophilia, a rare bleeding disorder Kyrie has had since birth. “He has a tough ... […]
- Sangamo Announces Treatment Of First Patient In Phase 1/2 Clinical Trial Of In Vivo Genome Editing Therapy For Hemophilia B on December 17, 2018 at 5:00 am
RICHMOND, Calif., Dec. 17, 2018 /PRNewswire/ -- Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomics medicines company, today announced treatment of the first patient in the Phase 1/2 clinical trial ... […]
- Global Hemophilia market size, trends, scope and regional outlook to 2018-2025 published by leading research firm on December 13, 2018 at 1:59 am
There are two major kinds of hemophilia namely Hemophilia A & Hemophilia B. Hemophilia A is considered to be five times more prevailing as compared to hemophilia B. Occurrence of hemophilia A is found ... […]
- Top Stocks Warren Buffett Just Sold on December 12, 2018 at 2:02 am
Warren Buffett's Berkshire Hathaway (NYSE: BRK-A) (NYSE: BRK-B) has been busy. In addition to swooping in ... acquisition of Bioverativ to gain exposure to the $10 billion-per-year hemophilia market e... […]
- Researchers refine gene therapy approach for hemophilia A on December 10, 2018 at 9:16 am
“Transgenic factor VIII expression was achieved in all patients at both vector doses.” Previous studies in hemophilia B have shown that a single peripheral vein administration of AAV vectors expressin... […]
- Continuous Infusion of Recombinant Activated Factor VII Safe, Effective in Management of Congenital Hemophilia on December 7, 2018 at 2:27 pm
Although rFVIIa is approved by the FDA for BI administration only for the treatment of bleeding episodes and the prevention of bleeding in surgical interventions or invasive procedures in patients wit... […]
via Bing News