A condition, known commonly as "black urine disease" or Alkaptonuria is a rare genetic disorder involving protein metabolism, and it has its root in the mutation of the homogentisate 1,2-dioxygenase gene, which in turn causes homogentisic acid accumulation in the body. The appearance of dark urine after exposure to air is due to this kind of accumulation; however, a variety of symptoms can be expected, such as joint stiffness, changes in pigmentation, and other long-term health complications. Although the prevalence has been estimated to be between 1 in 250,000 and 1 in 1 million people in the United States, its effects are indeed high on those affected.

Alkaptonuria is an autosomal recessive disease, meaning that the child must inherit a defective copy of the HGD gene from both parents. If both parents are carriers, their offspring have a 25% chance of inheriting two faulty genes and developing alkaptonuria. The condition is genetic but is often not diagnosed for years because it progresses slowly and its early symptoms appear to be harmless.

Symptoms of Alkaptonuria

The most characteristic and common initial symptom of alkaptonuria is dark urine. The reason for this is due to the fact that excess HGA is excreted in the urine and upon oxidation in the presence of air, it gives the urine a brown or black color. Though it is often considered cosmetic, the long-term accumulation of HGA within the connective tissues produces more complicated health problems.

Progressive joint pain and stiffness: The accumulation of HGA in cartilage leads to early-onset osteoarthritis, making movement increasingly difficult over time.

Skin and eye pigmentation changes: Affected individuals may develop bluish or grayish discoloration of the sclera (white part of the eye) and the skin, particularly in areas exposed to friction.

Cardiovascular and respiratory problems: With age, HGA accumulation can lead to valve calcifications in the heart and stiffening of connective tissues in the respiratory tract, which can cause problems in middle and old age.

Decreased mobility and spinal problems: The spine may become stiff and painful due to chronic cartilage degeneration.

These symptoms usually begin to manifest during adulthood, leading to severe complications in a person's 40s or 50s and significantly affecting the quality of their life.

How is Alkaptonuria Diagnosed?

Because of its rarity, alkaptonuria is often mistaken or overlooked early in life. However, there are several ways to confirm the condition:

Urine Testing: The gold standard in the diagnosis is the testing of urine samples for high levels of homogentisic acid via gas chromatography. In case of oxidation, which changes the color of urine to black, it is indicative of alkaptonuria.

Genetic Testing: Confirmatory genetic testing reveals mutations of the HGD gene to diagnose the condition conclusively.

Blood Tests: High levels of HGA in the blood can be used as further evidence.

Imaging Studies: X-rays and MRIs will expose cartilage and joint damage characteristic of alkaptonuria.

Management of Alkaptonuria: Is There A Cure?

At present, there is no cure for alkaptonuria; however, various treatment approaches can reduce its symptoms and slow the disease's progress:

Nitisinone Therapy: Nitisinone is a drug that inhibits the production of HGA. It has been shown to reduce HGA levels and slow tissue damage. However, it needs to be taken under close medical supervision because of potential side effects.

Low-Protein Diet: Since HGA is a byproduct of protein metabolism, reducing protein intake—especially foods rich in tyrosine and phenylalanine—may help decrease HGA production.

Pain Management: OTC pain relievers and anti-inflammatory medications can be used to relieve joint pain and stiffness.

Physical Therapy: Exercise regularly, as it may improve mobility and strengthen muscles, thus reducing strain on affected joints.

Surgical Interventions: Most people with alkaptonuria develop severe osteoarthritis necessitating joint replacement in their old age. Also, some may require heart valve replacement surgery if cardiovascular complications develop.

Life with Alkaptonuria

Although alkaptonuria is not fatal, it severely affects the quality of life. The progressive deterioration of the joints and associated symptoms can make everyday activities difficult, requiring lifestyle changes and medical interventions. The disease may cause premature aging of the joints, requiring walking aids and mobility assistance earlier than expected.

Ongoing research will continue to work on improving the treatment options by focusing on gene therapy and alternative enzyme replacement therapies. However, because of its rarity, the clinical trials and research remain sparse.

As genetic research advances, more hope for better management and possible curative approaches for alkaptonuria exists. Scientists are searching extensively for enzyme replacement therapies and innovative drugs that can target the root cause of the disorder. Being aware and being diagnosed early helps individuals better their condition and ultimately have better long-term health outcomes.

Alkaptonuria is a striking example of how one gene mutation can have widespread effects on the body. Though still a rare and often misunderstood condition, growing awareness and advances in treatment are paving the way for better care. If you or a loved one suspect symptoms of alkaptonuria, it is essential to seek early diagnosis and medical guidance to manage the disease effectively and preserve quality of life.

Waking up at night can make it difficult to fall back asleep, especially when the mind becomes alert and starts racing. Neuroscientist Andrew Huberman has suggested a simple eye-movement routine that he says may help people drift back to sleep. But does it actually work?

How Does Andrew Huberman’s Sleep Trick Work?

The routine is performed with the eyes closed:

• Slowly move the eyes to one side, then the other, followed by up and down.

• Trace a circle with the eyes, first counterclockwise and then clockwise.

• Point the eyes toward the nose and take a long exhale.

Huberman suggests repeating the sequence two to three times.

His theory is that the movements may interact with brain circuits involved in tracking the body's position, including pathways involving the eyes, brainstem and cerebellum.

Also read: Struggling With Sleep? Neurologist Shares 3 Simple Tips For Better Sleep Health

Sleep Experts Say The Idea Is Unproven

Shelby Harris, a psychologist and board-certified sleep expert, says there are reasonable grounds to try it, Women's World magazine reported.

“I think it’s a very reasonable thing to try. It’s free, low effort, carries essentially no risk and has solid reasons it could help,” Harris was quoted as saying.

She notes that sleep tends to become more fragmented with age.

“Sleep naturally becomes more fragmented with age, with less time in deep sleep and more time in the lighter stages where it’s easy to wake up,” Harris said.

Hormonal changes with age can also contribute to more fragile sleep in women. But a plausible explanation does not mean the technique has been proven.

Michael Grandner, a clinical psychologist and sleep researcher at the University of Arizona, told Inc.com that eye movements, balance signals, the brainstem and cerebellum all contribute to how the brain tracks the body's position in space.

However, he said he is “not aware of studies that have directly tested that chain of events, or clinical trials showing that this particular eye-movement exercise reliably shortens sleep onset.”

Brant Hasler, co-director of the Behavioral Sleep Medicine Training Program at the University of Pittsburgh School of Medicine, added that the technique does not resemble a validated behavioral sleep intervention.

A Relaxing Technique Not A Treatment

According to Grandner, the exercise may be better understood as a relaxation or focused-attention technique.

He said he would place it “closer to a relaxation, focused-attention, or mindfulness exercise than to an established treatment for insomnia.”

The repetitive movements could give the mind something neutral to focus on instead of worrying, planning for the next day or checking whether sleep has returned.

Further, Hasler said bedtime activities can be useful when they occupy the mind without becoming stimulating. The eye exercise could work in that way, he said, “regardless of any additional effects via proprioception.”

The slow breathing paired with the exercise may also help with relaxation.

It Could Backfire If You Try Too Hard

Hasler said expectancy effects could explain some positive experiences with the technique. Grandner also cautioned against repeatedly checking whether the trick is working.

If the exercise becomes another task to perform perfectly, “it could become another form of sleep effort, which can actually perpetuate insomnia,” he said.

Rabies is most often associated with dog-mediated transmission in humans, but the virus can infect a wide range of mammals. In 2026, unusual cases involving farm goats, beavers and Cape fur seals raised fresh questions about how rabies moves between species.

Since July 2026, multiple US jurisdictions have reported human rabies exposures involving known rabies vectors or animals in which rabies is less commonly reported. The CDC issued a health advisory on September 10 “in response to recent reports of increases in human exposures to rabid or possibly rabid animals.”

The concern is not limited to North America. At least 176 people had been bitten by rabid Cape fur seals along South Africa’s coastline by the end of 2025, while researchers have warned that the disease could spread to other marine mammal species.

In North Carolina in 2026, a wild skunk entered a pen containing baby goats, some of which later tested positive for rabies. Of the 284 people evaluated by local health departments, post-exposure prophylaxis (PEP) was recommended for 213. In Maryland, a 13-year-old boy was attacked by a beaver while swimming at a state park and required surgery for his injuries.

These cases raise a bigger question: Are unusual infections simply spillover from established rabies hosts, or can the virus establish sustained transmission in a new species? To understand this better, HealthandMe spoke to two experts.

Also read: US CDC Warns Of Rising Human Rabies Exposure Risk: How To Stay Safe

Are These New Rabies Hosts Or Spillover?

Dr Anish T S, Professor at the School of Public Health, Kerala University of Health Sciences, told HealthandMe that rabies can infect mammals, but an infected animal is not necessarily a reservoir host.

Genetic sequencing can help establish where an unusual infection came from and whether the virus is changing.

“So one thing that we can do is genetic analysis. If we are able to pick up these animals infected by rabies, we find what kind of rabies virus it is and do maybe a sequencing of the genome of this virus.”

“These kinds of analysis could be done still, but it is a question that whether this particular virus is changing its host or the virus is accumulating some kind of genetic mutations so that it can get maybe involved with some other animals. It can choose some other animals also as their host. It is actually a very pertinent question.”

The Cape fur seal cases add another dimension to this question, with sustained rabies transmission reported within the marine mammal population.

What Happens After Exposure?

Dr NK Ganguly, former Director General of the Indian Council of Medical Research (ICMR), told HealthandMe that rabies in goats is rare, while beaver exposures need particular caution.

“Beaver is one animal where we have to be very careful.”

Dr Anish said rabies can also present as paralytic or “dumb” rabies, which may not show classic signs and could lead people to handle or treat an infected animal without recognizing the risk.

Dr Ganguly stressed the need for prompt medical care after exposure.

“The rabies incubation period is around 10 days. So if somebody has been exposed, they should be immediately vaccinated. And if the exposure is with a bite or something at the upper limbs, then they need to be given an antiserum as well as vaccinated.”

“So depending on the exposure, you are given a vaccine which is available, and you are also given the cocktail of antibodies, the monoclonal antibodies, which act immediately.”

Why Wildlife And Livestock Surveillance Matters

Read More: Rabies Day Exclusive: ‘We Need To Target The Source’ For A Rabies-Free India By 2030, Says Veterinary Epidemiologist

Dr Ganguly said rabies can also circulate in wild and feral animals, including foxes, while cats and other species can also be infected.

He said surveillance should extend beyond dogs to domestic animals that are in close contact with them and to wildlife where feasible.

“Surveillance should include domestic animals also which are in close contact with the dogs.”

“There should be surveillance. There should be sentinel surveillance. We should carry out, if it is affordable.”

He also pointed to dog vaccination and sterilization, as well as bait vaccination for wildlife and stray animals.

Could The Virus Be Changing?

Dr Anish said unusual infections need investigation to determine whether they are isolated spillover events or linked to changes in the virus.

“The real issue is if the virus is changing much because of mutations. Because rabies virus is not that much notorious for mutations. That is why most of our vaccines are working.”

He said genetic studies could help answer whether existing vaccines and treatments would remain effective if significant mutations emerge.

“So the genetic studies of the virus may give us the answers to these questions.”

India’s Rabies Elimination Challenge

For India, the experts said the priority remains breaking established dog-mediated transmission chains before focusing on less common pathways.

“If you just look at the rabies situation in India, we are not even able to manage the pure dog-mediated rabies. That is, people are bitten by rabid dogs and people are getting infected, and we are not able to have maybe full coverage of vaccination, and all the other things are actually the biggest concern,” Dr Anish said.

Dr Ganguly added that surveillance should include domestic animals also which are in close contact with the dogs.

"But essentially, in the urban areas, the dog is the main animal, and we should—the Supreme Court has given now a lot of directions in this particular regard—that the dogs may be sterilized," the expert said.

The pet dogs need to be vaccinated and other stray dogs should be taken to facilities where they need to be sterilized and they need to be vaccinated, the experts said.

The current treatment course for high cholesterol is taking a daily tablet or regular injections over a long period. But instead, could a single treatment change the way high cholesterol is treated?

This possibility is being explored after a small first-in-human trial conducted by Cleveland Clinic found that one infusion of an experimental CRISPR gene-editing therapy lowered LDL, also called bad cholesterol, by about half and that the effect was still present a year later.

The treatment, called CTX310, is still experimental. The study involved just 15 people, so the findings are premature, not evidence that CRISPR can replace statins or other cholesterol medications.

About The Study

The Phase 1 trial included people with lipid disorders who had not responded adequately to existing medications.

Participants received a single infusion of CTX310, at different doses, and researchers followed them for 12 months.

At the highest dose, LDL cholesterol was reduced by 52.5% after one year, while triglycerides fell by 47.8%. The reductions seen earlier in the trial therefore persisted for at least 12 months.

Additionally, no serious adverse side effects related to the treatment were reported during the one-year follow-up. However, the researchers plan to continue monitoring participants for 15 years, as recommended for gene-editing therapies.

Also read: Inflammation May Be Quietly Changing Your Heart: Study Finds 43% Higher Risk Of Heart Attack & Stroke

How Does The CRISPR Treatment Work?

CTX310 operates differently compared to conventional cholesterol medicines. The treatment uses CRISPR-Cas9 gene editing to target ANGPTL3, a gene involved in regulating fats circulating in the blood.

The therapy delivers the gene-editing machinery to the liver, where it switches off ANGPTL3. Lower activity of this gene can reduce levels of LDL cholesterol and triglycerides.

The idea is that instead of using daily medicines to keep cholesterol in check, doctors could make a long-lasting genetic change.

Also read: Preeclampsia May End With Pregnancy. Your Heart Risk May Not

What Does It Mean For Statins?

Statins remain a reliable treatment approach for lowering LDL cholesterol and reducing cardiovascular risk. CTX310 has only been tested in a very small Phase 1 trial. Also, the study was primarily designed to examine the safety and explore whether the gene-editing treatment could produce a meaningful effect.

The fact that LDL remained lower after one year is promising and encouraging, but researchers still need to determine whether the treatment can safely maintain its effects over many years and, crucially, whether it reduces heart attacks, strokes and other cardiovascular events.

There is also a fundamental difference between cholesterol tablets and permanently altering a person’s DNA.

Promising Cholesterol Treatment Approach

High cholesterol is often a long-term condition. Depending on their risk, patients may need cholesterol-lowering treatment for many years.

If CRISPR becomes a reality, people may no longer have to stick to a chronic treatment strategy for managing cholesterol.

"Building upon the initial data presented in November 2025, the durability of the lipid-lowering effect was impressive," said Cleveland Clinic cardiologist Luke Laffin, M.D., first author of the study. "It is encouraging that there were no serious safety events related to CTX310 in the trial and in the year following treatment. We look forward to continuing to investigate this therapy in a larger number of patients."