
Left two panels: Hepatocyte-like cells (HLCs) differentiated from the stem cells of patients with hemophilia B show very low levels of clotting factor IX, or FIX, shown in white. Right two panels: After treating these same cell lines with a gene correction tool, FIX increased to healthy levels.
Credit: Salk Institute
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.
Learn more:Â Single injection treats hemophilia B for life, in proof-of-concept study
The Latest on: Hemophilia B
[google_news title=”” keyword=”hemophilia B” num_posts=”10″ blurb_length=”0″ show_thumb=”left”]
via Google News
The Latest on: Hemophilia B
- Global Hemophilia Treatment Market Report 2022 to 2030 - Featuring Ferring, Kedrion, Octapharma and Novo Nordis Among Otherson February 2, 2023 at 9:50 am
The "Hemophilia Treatment Market Size, Market Share, Application Analysis, Regional Outlook, Growth Trends, Key Players, Competitive Strategies and Forecasts, 2022 To 2030" ...
- Worldwide Hemophilia Treatment Industry to 2030 - by Product, Hemophilia Type and Regionon February 2, 2023 at 9:48 am
The global hemophilia treatment market is segmented by hemophilia type into Hemophilia A, Hemophilia B and others. Hemophilia is a genetic bleeding disorder caused due to deficiency or missing protein ...
- Hemophilia Treatment Market Expected to Grow at CAGR of 6.1% by 2027on February 1, 2023 at 3:07 am
The Insight Partners Latest Research for Report "Hemophilia Treatment Market to 2027” Focuses Global Analysis and Forecasts by Product (Plasma Derived ...
- Pfizer (PFE) Q4 2022 Earnings Call Transcripton January 31, 2023 at 4:00 pm
Q4 2022 Earnings Call Jan 31, 2023, 10:00 a.m. ET Operator Load Error Good day, everyone, and welcome to Pfizer's fourth quarter 2022 earnings conference call. Today's call is being recorded. At this ...
- Hemophilia Treatment Market to Exceed USD 20,507.92 Mn by 2028 Says, The Insight Partnerson January 30, 2023 at 5:35 am
The hemophilia treatment market was valued at US$ 12,797.36 million in 2019 and it is projected to reach US$ 20,507.92 million in 2027; it is expected to ...
- Gene therapy can transform life for people with hemophilia. But some patients don’t want it.on January 29, 2023 at 1:36 pm
Hemgenix is the first approved gene therapy in the US for hemophilia — and at $3.5 million per patient, it’s also the world’s most expensive drug.
- New gene therapy costs $3.5 million, but Greenville mothers explains why it may be worth iton January 24, 2023 at 3:04 pm
Three of her son’s were diagnosed with a rare blood disorder known as hemophilia B. It’s a genetic disorder that hinders their ability to produce a blood clotting protein. “The three boys ...
- World’s Most Expensive Drug Revives Push for New Payment Modelson January 23, 2023 at 2:25 am
A gene therapy considered to be the world’s most expensive drug raises questions about how to pay for it, and the federal agency overseeing Medicare and Medicaid could play a central role in ensuring ...
- Hemophilia Treatment Drugs Market Will Hold The Largest Industry Share Owing To The Rising Market Popularity In Global Countrieson January 22, 2023 at 5:23 pm
Hemophilia Treatment Drugs Market 2023 with 120 Pages Report and enhance with extents shares into sub-counties are ...
via Bing News