Researchers developed a new testing method to find better treatments for alkaptonuria, a rare genetic disease that affects how the body breaks down certain proteins. The current treatment has serious side effects, so scientists created a way to test thousands of existing medicines quickly. They found 30 drugs that might help restore the function of the broken enzyme that causes this disease. One drug showed particularly promising results, potentially offering hope for safer treatment options for people with this condition.

The Quick Take

  • What they studied: How to find existing medicines that could help fix a broken enzyme in people with alkaptonuria, a rare genetic disease
  • Who participated: This was a laboratory study using bacteria to test human enzyme variants, not a study with human participants
  • Key finding: 30 out of 2,320 FDA-approved drugs showed promise in restoring enzyme function, with one drug doubling the enzyme’s activity
  • What it means for you: If you have alkaptonuria, this research may lead to safer treatment options in the future, though more testing is needed

The Research Details

Scientists created a new laboratory test using bacteria that were modified to produce human versions of the broken enzyme found in alkaptonuria patients. They designed this test to quickly measure how well different medicines could restore the enzyme’s ability to do its job. The test was designed to handle thousands of different medicines at once, making it much faster than traditional methods. They validated their test to make sure it gave reliable and consistent results before using it to screen a large library of existing FDA-approved drugs.

This approach is important because it allows researchers to test many potential treatments quickly and efficiently. Instead of developing entirely new drugs from scratch, which takes decades and billions of dollars, they can identify existing medicines that might work for this rare disease.

The researchers carefully validated their testing method to ensure it was reliable and could detect meaningful differences. They used established quality measures and tested their system thoroughly before screening the drug library.

What the Results Show

Out of 2,320 FDA-approved drugs tested, the researchers identified 30 compounds that increased the activity of a common disease-causing enzyme variant by at least 3 times. One particular compound, called ‘Compound 21,’ showed especially promising results. When tested at different concentrations, this compound consistently doubled the enzyme’s activity compared to the untreated version. The researchers also used computer modeling to understand how this compound might work, suggesting it helps stabilize the enzyme structure at multiple points.

The new testing method also proved useful for ranking different genetic variants based on how much enzyme activity they retain. This could help doctors better understand how severe a patient’s condition might be based on their specific genetic mutation.

Current treatment for alkaptonuria involves a drug called nitisinone combined with a low-protein diet, but this approach causes serious side effects. This research represents a completely different approach - instead of blocking the pathway, these potential treatments would help restore the broken enzyme’s function.

This study was conducted entirely in laboratory bacteria, not in human cells or patients. The promising compounds need much more testing to determine if they’re safe and effective in people. The researchers also focused on just one common genetic variant, though the disease can be caused by many different mutations.

The Bottom Line

People with alkaptonuria should continue their current treatment as prescribed by their doctors. This research is still in very early stages and needs years of additional testing before any new treatments become available.

This research is most relevant for people with alkaptonuria and their families, as well as researchers working on rare genetic diseases. The testing method developed could also be useful for studying other genetic conditions.

If these results lead to new treatments, it would likely take 5-10 years of additional research and clinical trials before they become available to patients.

Want to Apply This Research?

  • Track current symptoms and side effects from existing treatments to establish baseline measurements
  • Continue following prescribed low-protein diet recommendations while staying informed about research developments
  • Regular monitoring of disease progression markers and treatment side effects to prepare for potential future treatment options

This research is in early laboratory stages and does not provide immediate treatment recommendations. People with alkaptonuria should continue their current prescribed treatments and consult their healthcare providers before making any changes to their medical care.