Therapy and medication #2

00:00:04: Welcome to Crystal Clear.

00:00:06: In this podcast, we share knowledge and experiences around cystinosis To help make living with this chronic disease a little more manageable And a bit easier in everyday life.

00:00:17: We're glad you are here With us!

00:00:31: how it works in the body, and why consistent therapy is crucial.

00:00:36: We'll also look at everyday challenges such as side effects —and offer practical tips on how to deal with them— including how cysteine levels are measured, Why they're a sensitive but important marker for treatment success And why any changes to dosage should always be carefully managed by a doctor.

00:00:53: We'll also take a look into the future with the first gene therapy studies and new cysteamine formulations, meaning the same active ingredient, cysteamine offered in a modified composition or dosage form to improve treatment.

00:01:07: I'm looking forward to speaking with my guest Dr.

00:01:10: Katarina Hoenn-Velner.

00:01:11: she is head of pediatric nephrology at Rohmed Klinikum Rosenheim founder of The Nationwide Cystinosis Outpatient Clinic In Germany And one of the world's leading specialists in cystinosis.

00:01:22: Hello, Dr.

00:01:23: Hoenn Felner?

00:01:24: Hello!

00:01:25: Thank you very much for having me here today and for this conversation.

00:01:30: So what medications are available for the treatment of cystinosis?

00:01:34: Unfortunately so far there is only one drug therapy available for treating cystinosus.

00:01:40: That's Cystiamine.

00:01:42: Cystiumene unfortunately has a drawback It isn't well tolerated but it is a sulfur compound.

00:01:48: This sulfur compounds leads to what we call halitosis.

00:01:52: That means two hours after taking it, the sulfur is exhaled and causes an unpleasant odor.

00:01:57: It should be noted that not every patient smells —it's a bit like garlic— some people smell others do not but overall its rather unpleasant side effect.

00:02:07: Currently another medication has been researched – it was already quite far along in development.

00:02:12: It also assists immune therapy…but with this one patients don't smell.

00:02:17: Furthermore, there is a formulation being developed that only needs to be taken once-a day.

00:02:21: Also assistiamine preparation and last but not least There's the first gene therapy study for this condition currently recruiting patients in The United States.

00:02:30: So while research into possible future alternatives Is underway In the united

00:02:35: states

00:02:35: Sistiamine remains the central And established form of Therapy here in Germany.

00:02:41: How does Sistiumine Therapy work?

00:02:43: Well, you might imagine it like this.

00:02:46: Think of the cell as an aquarium and inside this aquarium there is a small pink ball that is the lysosome.

00:02:53: The lysosomes acts like a filter keeping the aquarium clean.

00:02:56: now Sistine This is an amino acid that we need to live Diffuses into this ball in a healthy cell.

00:03:03: It can also diffuse back out of this little pink ball into the aquarium.

00:03:07: In cystinosis, however the filter on one side is not permeable.

00:03:11: This means cysteine accumulates inside the pink ball.

00:03:15: eventually so much builds up that the ball can no longer perform its filtering function and The entire aquarium.

00:03:21: in this case the cell falls into disorder And ultimately dies.

00:03:25: Cystiumene has the ability to diffuse Into the pinkball.

00:03:29: it binds To the cysteines.

00:03:30: then the cystein Can be transported out through other channels.

00:03:34: That is the basic mechanism.

00:03:35: We have lysosomes in all our body cells, this means that in cystinosis – ALL organs and ultimately ALL cells are affected!

00:03:43: Against this background it must also be said that cystiumene is unfortunately a lifelong medication.

00:03:49: It must be taken for life And even with this therapy there IS no cure Only a delay in progression of disease.

00:03:56: Which medications are available?

00:03:58: Here in Germany we have two approved medications.

00:04:02: One of them is, let's say a relatively old medication.

00:04:06: It was the first one to be approved back in nineteen ninety-seven.

00:04:10: it is called Cystagon.

00:04:12: The other is Procispy.

00:04:14: Both are cysteamine preparations.

00:04:16: Cystogon must be taken consistently every six hours.

00:04:20: Procispe on the other hand Is so-called extended release formulation meaning that only needs to be taken twice a day Every twelve hours.

00:04:28: So the difference between the two medications lies in how often they need to be taken, but the efficacy of both is the same.

00:04:35: How should cystia mean medication be taken?

00:04:38: What is

00:04:39: recommended?".

00:04:40: Well from a manufacturer's perspective Both Cystagon and Prosyspii are recommended on an empty stomach or before meals.

00:04:49: However for most patients this isn't feasible.

00:04:52: Cystiumine medication has, as mentioned, significant side effects.

00:04:56: It can cause nausea and vomiting.

00:04:59: Taking food beforehand or alongside the medication often helps it to be better tolerated.

00:05:04: However especially when taking prosispy you need to be careful about what you eat because prosispi is an extended release preparation.

00:05:14: It's encapsulated should ideally not dissolve in your stomach.

00:05:18: Patients also need bicarbonate and citrate, And these medications for example cannot be taken together with prosispy.

00:05:25: At this point I would like to particularly highlight the role of patient self-help groups Especially when it comes to side effects of cystiamine.

00:05:34: Self help group can very helpful tips and tricks Because people there speak from personal experience.

00:05:41: Are any problems with administration When a peg is in place?

00:05:45: That's a gastric tube.

00:05:47: A peg, which stands for percutaneous endoscopic gastrostomy is often placed in children shortly after diagnosis.

00:05:55: When children are diagnosed and my colleague Dr.

00:05:58: Wool will also address this in her episode they often have a very high fluid requirement.

00:06:03: they need to take relatively large amounts of medication, including cystiumene which does not taste very good.

00:06:09: In these cases a tube is helpful.

00:06:11: it's placed through the abdomen into stomach and thru it medications and fluids can be administered without child having drink them.

00:06:19: however one should careful.

00:06:20: cystogon can dissolved in water then administered trough the tube but with prosispy.

00:06:25: its important check advance whether small pellets pass though This should be discussed with the nephrologist beforehand to ensure there are no difficulties.

00:06:59: This means you have to decide individually how quickly the dose can be increased, however The goal should be to reach the final dose within six-to eight weeks and To ensure that the target dose is actually achieved.

00:07:11: How can cystia mean therapy?

00:07:12: Be monitored in other words.

00:07:14: How do I know that I'm taking the right dose?

00:07:17: Yes when it comes to monitoring cystinosis or a Cysteamine therapy There's currently only one method available the so called cysteine level.

00:07:27: Coming back to the image of the aquarium with a pink ball, The cysteine level measures the cystein content inside that pink ball while on cysteamine therapy.

00:07:37: As we already mentioned We have lysosomes in all cells including white blood cells.

00:07:42: This means I can simply take a blood sample and measure the Cysteine Level In the Lysosomes Of White Blood Cells.

00:07:49: However what must be kept in mind is Unlike, for example a diabetic patient where I have long term value like HBA A-one C and can say the patient has been slightly off track over past three months.

00:08:02: The cysteine level does not work that way.

00:08:05: The cysteine level only gives me information about the most recent dose of cystogon or prosispy.

00:08:11: This also means that if I have a level that is perhaps not so good, i do not necessarily change the therapy straight away and equally If the Level Is Good ,I Do Not Reduce The Dose.

00:08:22: In Germany there are three laboratories That Measure The Cysteine Level.

00:08:26: These three laboratories use different methods, so the values are not directly comparable.

00:08:32: But what is very important is that the blood sample must be taken consistently six hours after taking cystogon or twelve hours after making prosispy.

00:08:41: regardless of method The blood then must arrive at laboratory within twenty-four hours and process there.

00:08:48: Otherwise level isn't usable.

00:08:50: So it's quite complex but not entirely reliable.

00:08:53: It does provide an indication.

00:08:55: Additionally, there is also the option of weight-based dosage calculations which can be used to check whether you are within the range appropriate for your bodyweight and height.

00:09:05: And how often should this cysteine level be measured?

00:09:08: Well...for young children especially when therapy is being gradually introduced.

00:09:13: it should be done regularly.

00:09:14: Also as they grow and gain weight The dose can adjusted about four times per year.

00:09:20: For adult patients who are no longer growing and hopefully, no-longer gaining much weight once or twice a year is actually sufficient.

00:09:28: And of course it also gives patients a certain reassurance that despite this very demanding therapy they're within the normal range.

00:09:35: With such complex therapy what side effects should one expect?

00:09:40: Yes as already mentioned cystiamine is very effective but has quite significant side effects.

00:09:48: One of the most common are so-called gastrointestinal side effects, that is nausea, vomiting and diarrhea.

00:09:56: The second side effect is halitosis—the odor that occurs two hours after taking medication.

00:10:02: Additionally headaches can occur…and something patients should definitely watch out for!

00:10:08: In very rare cases there's a condition called pseudotumor cerebri meaning increased intracranial pressure.

00:10:16: Signs of this include recurring headaches, and above all vomiting in the morning on an empty stomach.

00:10:22: What

00:10:22: can be done about gastrointestinal symptoms?

00:10:25: As you mentioned these include complaints such as bloating diarrhea constipation nausea heartburn.

00:10:34: Well one option is to look at when and how a medication has taken.

00:10:39: there's some flexibility here.

00:10:41: You do not have to say, I take my cystiamine at exactly eight AM or six AM.

00:10:47: There is a bit of leeway as long the intervals between doses are maintained.

00:10:51: that's one thing.

00:10:53: The second is certain symptoms can also be treated with medication for example stomach pain.

00:10:59: With diarrhea it sometimes more difficult and in some cases dose may need to be reused temporarily paused.

00:11:06: Again, I would like to refer to self-help groups and the recommendations from those affected which are often very helpful.

00:11:13: How can one deal with halitosis?

00:11:16: The bad breath!

00:11:17: And what could be done about it?

00:11:19: Halitosis is caused by the sulfur compound contained in cystiumene... ...and sulfur is neutralized by zinc.

00:11:27: So if you use zinc containing mouthwash You can at least reduce the bad breath or zinc containing chewing gum.

00:11:34: There is also the option of chlorophyll, wheatgrass, wheat grass powder and some children use mint.

00:11:41: Personally I believe what's very important to be open about it because that isn't the patient who smells but medication which means if people around them know this medication then a different situation than when they think someone has bad breath.

00:11:58: What does it mean?

00:12:01: dosage?

00:12:04: Most importantly, you should neither overdose nor underdose.

00:12:08: When it comes to overdosing there is a maximum upper limit of ninety milligrams per kilogram per day but under dosing is equally problematic because cystia mean therapy as I said stabilizes those little aquariums ourselves and keeps them functioning.

00:12:25: this means You should always check where you stand firstly As mentioned using the cysteine level and also by calculating the dose based on body weight or body surface area.

00:12:36: And when does cystiumine need to be stopped?

00:12:39: Cystiumene must be stopped the moment a pregnancy is confirmed, as my colleague Dr.

00:12:45: Choi explains in her episode – not when someone is trying to become pregnant but once the pregnancy has been confirmed.

00:12:52: Cystiamine should then be paused for entire duration of the pregnancy.

00:12:57: There are also other situations, such as a kidney transplant where cysteamine is stopped before the procedure.

00:13:04: Therapy can be restarted after the transplant whenever the patient is ready.

00:13:08: Since a transplant is also a significant procedure you should make sure to restart the therapy in way that does not cause nausea but it can be started immediately.

00:13:19: Regarding gastrointestinal side effects, it should also be noted that cysteamine can cause ulcerations or irritation in the gastro-intestinal tract.

00:13:28: Ulcers is in stomach and small intestine.

00:13:31: In these cases therapy must be paused And the ulcer or gastritis treated.

00:13:36: There's a very rare side effect with prosispy Fibrosine colonopathy.

00:13:42: In this case therapy must have been paused or discontinued.

00:13:46: What happens during a cysteamine rate?

00:13:50: That's a very good question, one we are frequently confronted with.

00:13:54: Especially by young women who want to become pregnant We don't know exactly.

00:13:59: I think that this break particularly in the context of pregnancy is well tolerated and if The patients were very adherent beforehand it does not pose A problem.

00:14:10: overall however One should try To adhere to This therapy even though It Is currently still Very demanding.

00:14:16: We hope that will change soon and at least the formulation doesn't cause odor to make it easier for the rest of one's life.

00:14:26: Dr.

00:14:27: Hoenn-Felner, how did you come specifically on cystinosis?

00:14:32: There was a patient in the patient population at the Children's Hospital in Traunstein.

00:14:37: She is also the first patient I ever saw.

00:14:41: I completed my pediatric nephrology training at the University Hospital in Mines where we had no patients with cystinosis.

00:14:49: Then, the question came up of how her care could continue?

00:14:52: The patient's has previously been treated by Professor Harms and Munster who then retired out-of.

00:14:57: that idea of an interdisciplinary Outpatient Clinic emerged At time together with Ms.

00:15:03: Sprote Who founded the self help group.

00:15:10: How wonderful!

00:15:12: Everyone I've spoken to so far has described you as the leading specialist in cystinosis and a driving force.

00:15:19: What does that do?

00:15:21: Does it make your proud, or even a little

00:15:23: happy?".

00:15:24: Yes...it makes me very happy because Cystinosis is such rare condition….

00:15:30: It's truly great joy.

00:15:32: we have managed to interest other specialists.

00:15:39: Thank you very much Dr.

00:15:40: Katerina Hoenn-Velner, head of pediatric nephrology at Rohmed Clinicum Rosenheim and founder the nationwide cystinosis outpatient clinic in Germany And we also received a message from a mother

00:15:53: Giving your own child medication every two to three hours Every day seven days a week until they are old enough.

00:16:02: take it themselves is real challenge.

00:16:05: To manage this, certain medical aids such as a feeding tube in our case are unavoidable since consistent intake is crucial for a

00:16:14: positive

00:16:14: prognosis later on.

00:16:16: We have been able to adapt the therapy to our lives through good care and networking.

00:16:22: Our everyday life has become livable again!

00:16:28: It is a lifelong therapy that those affected depend on permanently.

00:16:38: In Germany, two preparations are approved—cystigan and prosispy.

00:16:43: They're equally effective but differ in how often they need to be taken.

00:16:48: Both under-dosing and overdosing should be strictly avoided.

00:16:52: Therapy can be monitored and adjusted using the cyst team level of blood as well as weight & height based dosage parameters.

00:17:00: At same time there's reason for hope.

00:17:03: New therapeutic approaches are currently in development.

00:17:06: Thank you for listening!

00:17:07: If you'd like to learn more, the Cystenosis Foundation offers further podcast episodes and videos that provide helpful information and support for everyday life with cystenosis.

00:17:17: Do take a look And see you next episode.